The University of British Columbia, commonly referred to as UBC, is a public research university with campuses and facilities in the province of British Columbia, Canada.Founded in 1908 as the McGill University College of British Columbia, the university became independent and adopted its current name in 1915. It is the oldest institution of higher learning in British Columbia and enrolls over 58,000 students at its Vancouver and Okanagan Valley campuses. UBC's 4.02 km2 Vancouver campus is located within the University Endowment Lands, about 10 km from Downtown Vancouver. The 2.09 km2 Kelowna campus, acquired in 2005, is located in the Okanagan Valley.UBC is ranked 30th in the world according to U.S. News & World Report 's 2015 rankings and eighth among universities outside the United States by Newsweek. UBC faculty, alumni, and researchers have won seven Nobel Prizes, 68 Rhodes Scholarships, 65 Olympic medals, 180 fellowships to the Royal Society of Canada, and alumni include two Canadian prime ministers. UBC is a research-intensive university that funds more than 8,000 projects with its $519 million research budget.UBC is a non-sectarian and coeducational institution, with more than 275,000 living alumni in 120 countries. The university is a member of Universitas 21, the Association of Universities and Colleges of Canada, the Association of Southeast Asian Institutions of Higher Learning, the International Association of Universities, the U15 and the only Canadian member of the Association of Pacific Rim Universities. The university's varsity teams, known as the Thunderbirds in Vancouver and the Heat in the Okanagan, compete in the Canada West Universities Athletic Association of the Canadian Interuniversity Sport. Wikipedia.
Veenstra G.,University of British Columbia
International Journal of Health Services | Year: 2012
Inspired by Bourdieu's theories on various forms of capital, conversions among them, and the fields (social spaces) delineated by possession of them, the authors investigate distinct and interconnected effects of cultural, economic, and social capitals on risk of mortality. Using 35 years of longitudinal data from the Alameda County Study (n = 6,157), they created discrete-time hazard models to predict all-cause mortality from educational attainment (institutionalized cultural capital), household income (economic capital), and different forms of personal ties (social capital). The results show that education, income, having three or more close friends, regularity of church attendance, and participation in social/recreational groups were all negatively and significantly associated with risk of mortality. Income mediated a significant portion of the education effect. None of the personal ties variables mediated the effects of education or income. Relative composition of the sum total of education and income did not have an effect. Lastly, examination of statistical interactions between capitals determined that protective effects of church attendance and participation in community betterment groups applied only to non-wealthy people. These findings speak to the structure of the U.S. social space within which health-delimiting relationally defined social classes may be made manifest. © 2012, Baywood Publishing Co., Inc.
Manges A.R.,University of British Columbia
Clinical Microbiology and Infection | Year: 2016
Extraintestinal pathogenic Escherichia coli (ExPEC) is the most common cause of community-acquired and hospital-acquired extraintestinal infections. The hypothesis that human ExPEC may have a food animal reservoir has been a topic of investigation by multiple groups around the world. Experimental studies showing the shared pathogenic potential of human ExPEC and avian pathogenic E. coli suggest that these extraintestinal E. coli may be derived from the same bacterial lineages or share common evolutionary roots. The consistent observation of specific human ExPEC lineages in poultry or poultry products, and rarely in other meat commodities, supports the hypothesis that there may be a poultry reservoir for human ExPEC. The time lag between human ExPEC acquisition (in the intestine) and infection is the fundamental challenge facing studies attempting to attribute ExPEC transmission to poultry or other environmental sources. Even whole genome sequencing efforts to address attribution will struggle with defining meaningful genetic relationships outside of a discrete food-borne outbreak setting. However, if even a fraction of all human ExPEC infections, especially antimicrobial-resistant ExPEC infections, is attributable to the introduction of multidrug-resistant ExPEC lineages through contaminated food product(s), the relevance to public health, food animal production and food safety will be significant. © 2016 European Society of Clinical Microbiology and Infectious Diseases.
Whitehouse M.R.,University of British Columbia
The bone & joint journal | Year: 2013
Hip arthrodesis remains a viable surgical technique in well selected patients, typically the young manual labourer with isolated unilateral hip disease. Despite this, its popularity with patients and surgeons has decreased due to the evolution of hip replacement, and is seldom chosen by young adult patients today. The surgeon is more likely to encounter a patient who requests conversion to total hip replacement (THR). The most common indications are a painful pseudarthrosis, back pain, ipsilateral knee pain or contralateral hip pain. Occasionally the patient will request conversion because of difficulty with activities of daily living, body image and perceived cosmesis. The technique of conversion and a discussion of the results are presented.
Bell K.,University of British Columbia
Global Public Health | Year: 2015
In recent years, HIV/AIDS programming has been transformed by an ostensibly ‘new’ procedure: male circumcision. This article examines the rise of male circumcision as the ‘right’ HIV prevention tool. Treating this controversial topic as a ‘matter of concern’ rather than a ‘matter of fact’, I examine the reasons why male circumcision came to be seen as a partial solution to the problem of HIV transmission in the twenty-first century and to what effect. Grounded in a close reading of the primary literature, I suggest that the embrace of male circumcision in HIV prevention must be understood in relation to three factors: (1) the rise of evidence-based medicine as the dominant paradigm for conceptualising medical knowledge, (2) the fraught politics of HIV/AIDS research and funding, which made the possibility of a biomedical intervention attractive and (3) underlying assumptions about the nature of African ‘culture’ and ‘sexuality’. I conclude by stressing the need to expand the parameters of the debate beyond the current polarised landscape, which presents us with a problematic either/or scenario regarding the efficacy of male circumcision. © 2014 Taylor & Francis.
Martin-Matthews A.,University of British Columbia
Canadian Journal on Aging | Year: 2011
This analysis reviews the ways in which both the experience of widowhood in old age and the nature of research on widowhood have changed since the publication of the book Widowhood in Later Life in 1991. Patterns of decline in widowhood in both its duration and incidence in later life are examined. Widowhood research has advanced conceptually by moving beyond understanding widowhood solely in terms of role loss. Life course perspectives, and concepts of multiple narratives and of resilience, have also contributed to the field. New methodologies, including prospective and longitudinal designs involving larger data sets, and more in-depth qualitative studies, have advanced our understanding of complexities and variations in widowhood. These include issues of gender and ethnocultural diversity, as well as the intersection of wealth, health, and class. This article also examines how patterns of labour force affiliation, social policy, and the changing nature of marriage shape widowhood in later life. © Canadian Association on Gerontology 2011.
Eddy A.A.,University of British Columbia
Kidney International Supplements | Year: 2014
The common pathogenetic pathway of progressive injury in patients with chronic kidney disease (CKD) is epitomized as normal kidney parenchymal destruction due to scarring (fibrosis). Understanding the fundamental pathways that lead to renal fibrosis is essential in order to develop better therapeutic options for human CKD. Although complex, four cellular responses are pivotal. (1) An interstitial inflammatory response that has multiple consequences - some harmful and others healing. (2) The appearance of a unique interstitial cell population of myofibroblasts, primarily derived from kidney stromal cells (fibroblasts and pericytes), that are the primary source of the various extracellular matrix proteins that form interstitial scars. (3) Tubular epithelial cells that have variable and time-dependent roles as early responders to injury and later as victims of fibrosis due to the loss of their regenerative abilities. (4) Loss of interstitial capillary integrity that compromises oxygen delivery and leads to a vicious cascade of hypoxia-oxidant stress that accentuates injury and fibrosis. In the absence of adequate angiogenic responses, a healthy interstitial capillary network is not maintained. The fibrotic 'scar' that typifies CKD is an interesting consortium of multifunctional macromolecules that not only change in composition and structure over time, but can be degraded via extracellular and intracellular proteases. Although transforming growth factor beta appears to be the primary driver of kidney fibrosis, a vast array of additional molecules may have modulating roles. The importance of genetic and epigenetic factors is increasingly appreciated. An intriguing but incompletely understood cardiorenal syndrome underlies the high morbidity and mortality rates that develop in association with progressive kidney fibrosis. © 2014 International Society of Nephrology.
Tan W.C.,University of British Columbia
Current Opinion in Pulmonary Medicine | Year: 2011
Purpose of review: The burden of chronic obstructive pulmonary disease (COPD) is rapidly growing in the Asia-Pacific region. There is the need for region-specific research and analysis of the epidemiology of COPD to raise awareness of the disease and highlight its causes. Such information is essential to for the development of effective national health policies to ensure evidence-based deployment of finite healthcare resources in the prevention and management of COPD. Recent findings: Recent population-based epidemiological studies have confirmed previous assumptions that COPD in the Asia-Pacific region is as prevalent as in the mature economies of the western world. The greatest numbers of deaths and hospitalizations from COPD are concentrated in this populous region of the world. The patterns in trends in mortality and hospitalization in the past 10 years in Asia-Pacific countries show a spectrum from the 'mature' to the 'evolving' and are likely related to the combined effects of cigarette smoking and nonsmoking risk factors. Gross underdiagnosis of COPD and underutilization of spirometry further contribute to burden and are barriers to appropriate and timely management of COPD. Summary: COPD is a common disease with a large disease burden throughout the Asia-Pacific region. Effective public health preventive measures coupled with timely case detection are needed for the reversal of trends and the reduction of disease burden. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
John Livesley W.,University of British Columbia
Journal of Personality Disorders | Year: 2011
An empirically-based classification is proposed based on studies of the phenotypic structure and genetic architecture of personality disorder. The proposed system has two parts: (1) a definition of general personality disorder, and (2) a system for diagnosing different forms of disorder. General personality disorder is conceptualized as a pervasive disturbance in the overall structure and organization of the personality system that is manifested as the failure to establish a coherent self-system and the capacity for adaptive interpersonal and social behavior. Different forms of disorder are represented by a dimensional system consisting of 30 primary traits organized into four higher-order domains. The system is intended to offer a systematic and comprehensive diagnosis of personality disorder for clinical and research purposes. It is also intended to be used in a flexible but prescribed way to provide a diagnostic assessment tailored to different assessment needs. © 2011 The Guilford Press.
Hauert C.,University of British Columbia
Journal of Theoretical Biology | Year: 2010
Public goods games have become the mathematical metaphor for game theoretical investigations of cooperative behavior in groups of interacting individuals. Cooperation is a conundrum because cooperators make a sacrifice to benefit others at some cost to themselves. Exploiters or defectors reap the benefits and forgo costs. Despite the fact that groups of cooperators outperform groups of defectors, Darwinian selection or utilitarian principles based on rational choice should favor defectors. In order to overcome this social dilemma, much effort has been expended for investigations pertaining to punishment and sanctioning measures against defectors. Interestingly, the complementary approach to create positive incentives and to reward cooperation has received considerably less attention-despite being heavily advocated in education and social sciences for increasing productivity or preventing conflicts. Here we show that rewards can indeed stimulate cooperation in interaction groups of arbitrary size but, in contrast to punishment, fail to stabilize it. In both cases, however, reputation is essential. The combination of reward and reputation result in complex dynamics dominated by unpredictable oscillations. © 2010 Elsevier Ltd.
Kuus M.,University of British Columbia
Annals of the Association of American Geographers | Year: 2011
This article analyzes geopolitics as a bureaucratic practice conducted by career policy professionals. Empirically, I investigate how the European Neighbourhood Policy (ENP) continuously produces and transforms the geopolitical category of "Europe" inside the European Union's (EU) policymaking bureaucracy-or EUrope as it is called colloquially. Drawing in part from forty-six interviews with thirty-five policy professionals, the article elucidates how these professionals use the concept of Europe in their daily work on ENP-not how they understand the concept intellectually but how they actually deploy it in policy discussions. Theoretically, I clarify how practical geopolitics operates through banal assumptions that are activated occasionally but present in an unremarkable way every day, how geopolitical categories are problematized inside policymaking bureaucracies, and how grand geopolitical visions are given specific technical content within everyday policy processes. The EU is an important example of this process because of its sheer global weight as well as the novel transnational character of its institutions. The argument advances two related strands of work in human geography: one on the role of public policy in producing social realities and the other on the capacity of specific individuals to shape geopolitical discourses. © 2011 by Association of American Geographers Initial submission.
Bumpus A.G.,University of British Columbia
Antipode | Year: 2011
This paper examines the socio-natural relations inherent in the commodification of carbon reductions as they are generated in energy-based carbon offset project activities, and abstracted to wider market systems. The ability to commodify carbon reductions takes place through a socionatural-technical complex that is defined by the material nature of technology's interaction with the atmosphere, local social processes and the evolving governing systems of carbon markets. Carbon is not unproblematically commodified: some projects and technologies allow a more cooperative commodification than others. The examples of a hydroelectricity plant and an improved cookstove project in Honduras are used as empirical case studies to illustrate the difficulties and opportunities associated with the relational aspects of carbon commodification. Drawing upon select literatures from post-structural thought to complement the principal lens of a more structural, materiality of nature analysis, the paper also outlines the reasons why carbon offset reform is needed if offsets are to more progressively engage debates about climate mitigation and North-South development. © 2011 The Author Antipode © 2011 Editorial Board of Antipode.
Lee M.,University of British Columbia
Current Protein and Peptide Science | Year: 2013
Reciprocal interactions between cells caused by release of soluble factors are essential for brain function. So far, little attention has been paid to interactions between neurons and glia. However, in the last few decades, studies regarding such interactions have given us some important clues about possible mechanisms underlying degenerative processes in neurological diseases such as Alzheimer's disease and Parkinson's disease. Activated microglia and markers of inflammatory reactions have been consistently found in the post-mortem brains of diseased patients. But it has not been clearly understood how microglia respond to neurotransmitters released from neurons during disease progression. The main purpose of this review is to summarize studies performed on neurotransmitter receptor expression in microglia, and the effects of their activation on microglial-mediated neuroinflammation. A possible mechanism underlying transmitter-mediated modulation of microglial response is also suggested. Microglia express receptors for neurotransmitters such as ATP, adenosine, glutamate, GABA, acetylcholine, dopamine and adrenaline. Activation of GABA, cholinergic and adrenergic receptors suppresses microglial responses, whereas activation of ATP or adenosine receptors activates them. This latter effect may be due primarily to activation of a Ca2+-signaling pathway which, in turn, results in activation of MAP kinases and NFkB proteins with the release of proinflammatory factors. However, glutamate and dopamine are both pro-and anti-inflammatory depending on the receptor subtypes expressed in microglia. More detailed studies on downstream receptor-signaling cascades are needed to understand the roles of neurotransmitters in controlling neuron-microglia interactions during inflammatory processes in disease progression. Such knowledge may suggest new methods of treatment. © 2013 Bentham Science Publishers.
Koehle M.S.,University of British Columbia
European journal of emergency medicine : official journal of the European Society for Emergency Medicine | Year: 2010
The clinical evaluation of acute mountain sickness (AMS) is often performed in remote settings with minimal equipment. The purpose of this study was to examine the utility of heart rate variability and other cardiovascular parameters in a high-altitude clinical setting. Forty-one participants were recruited from the patient population of the clinic, and from festivalgoers [those who attended the Janai Purnima festival held at Lake Gosainkunda (4380&x2009;m) in Langtang, Nepal] in the vicinity of the clinic. Twenty-one participants were diagnosed with AMS; remaining participants were free from altitude illness. Heart rate variability (both time and frequency domain measures), arterial oxygen saturation (SpO2), blood pressure and Lake Louise Score were evaluated in all the participants. Oxygen saturation and diastolic blood pressure were negatively and positively correlated with Lake Louise Score, respectively. Receiver operating characteristic analysis indicated that an SpO2 of 86% or greater was associated with a very low likelihood of AMS at this altitude. No heart rate variability parameters were different in the AMS group as compared with the control group. In conclusion, in patients with SpO2 of 86% or more at 4380&x2009;m or higher, the likelihood of AMS is low. Diastolic blood pressure correlated with AMS severity, whereas heart rate variability was not useful in the diagnosis of AMS.
Domhoff G.W.,University of California at Santa Cruz |
Fox K.C.R.,University of British Columbia
Consciousness and Cognition | Year: 2015
This article argues that the default network, augmented by secondary visual and sensorimotor cortices, is the likely neural correlate of dreaming. This hypothesis is based on a synthesis of work on dream content, the findings on the contents and neural correlates of mind-wandering, and the results from EEG and neuroimaging studies of REM sleep. Relying on studies in the 1970s that serendipitously discovered episodes of dreaming during waking mind-wandering, this article presents the seemingly counterintuitive hypothesis that the neural correlates for dreaming could be further specified in the process of carrying out EEG/fMRI studies of mind-wandering and default network activity. This hypothesis could be tested by asking participants for experiential reports during moments of differentially high levels of default network activation, as indicated by mixed EEG/fMRI criteria. Evidence from earlier EEG/fMRI studies of mind-wandering and from laboratory studies of dreaming during the sleep-onset process is used to support the argument. © 2015 Elsevier Inc.
Choptuik M.W.,University of British Columbia |
Pretorius F.,Princeton University
Physical Review Letters | Year: 2010
We present results from numerical solution of the Einstein field equations describing the head-on collision of two solitons boosted to ultrarelativistic energies. We show, for the first time, that at sufficiently high energies the collision leads to black hole formation, consistent with hoop-conjecture arguments. This implies that the nonlinear gravitational interaction between the kinetic energy of the solitons causes gravitational collapse, and that arguments for black hole formation in super-Planck scale particle collisions are robust. © 2010 The American Physical Society.
Wan M.,Northwestern Polytechnical University |
Altintas Y.,University of British Columbia
International Journal of Machine Tools and Manufacture | Year: 2014
This paper presents the mechanics and dynamics of thread milling operations. The tool follows a helical path around the wall of the pre-machined hole in thread milling, which has varying tool-part engagement and cut area during one threading cycle. The variation of cut area that reflects the kinematics of threading as well as structural vibrations is modeled along the helical, threading path. The mechanics of the process are first experimentally proven, followed by the formulation of dynamic thread milling which is periodic in threading cycle, in a semi-discrete time domain. The stability of the operation is predicted as a function of spindle speed, axial depth of cut, cutter path and tool geometry. The mechanics and stability models are experimentally proven in opening M16×2 threads with a five-fluted helical tool on a Steel AISI1045 workpiece. © 2014 Elsevier Ltd.
Gibson W.T.,University of British Columbia
Clinical Genetics | Year: 2015
Loss-of-function mutations in APOC3, triglycerides, and coronary disease. TG & HDL Working Group of the NHLBI Exome Sequencing Project (2014) N Engl J Med 371:22-31 Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. Jørgensen et al. (2014) N Engl J Med 371:32-41 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Keeling P.J.,University of British Columbia
Cold Spring Harbor Perspectives in Biology | Year: 2014
Evolutionary hypotheses are correctly interpreted as products of the data they set out to explain, but they are less often recognized as being heavily influenced by other factors. Oneof these is the history of preceding thought, and here I look backon historically important changes in our thinking about the role of endosymbiosis in the origin of eukaryotic cells. Specifically, the modern emphasis on endosymbiotic explanations for numerous eukaryotic features, including the cell itself (the so-called chimeric hypotheses), can be seen not only as resulting from the advent of molecular and genomic data, but also from the intellectual acceptance of the endosymbiotic origin of mitochondria and plastids. This transformative ideamay have undulyaffected howother aspects of the eukaryotic cell are explained, in effect priming us to accept endosymbiotic explanations for endogenous processes. Molecular and genomic data, which were originally harnessed to answer questions about cell evolution, nowso dominate our thinking that they largely define the question, and the original questions about howeukaryotic cellular architecture evolved have been neglected. This is unfortunate because, as Roger Stanier pointed out, these cellular changes represent life's "greatest single evolutionary discontinuity," and on this basis I advocate a return to emphasizing evolutionary cell biology when thinking about the origin of eukaryotes, and suggest that endogenous explanations will prevail when we refocus on the evolution of the cell. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.
Thachuk C.,University of British Columbia
Theoretical Computer Science | Year: 2013
We study the problem of indexing text with wildcard positions, motivated by the challenge of aligning sequencing data to large genomes that contain millions of single nucleotide polymorphisms (SNPs) - positions known to differ between individuals. SNPs modeled as wildcards can lead to more informed and biologically relevant alignments. We improve the space complexity while maintaining the query time complexity of previous approaches by giving a compressed index requiring 2nHk(T)+o(nlogσ)+O(n+dlogn) bits for a text T of length n over an alphabet of size σ containing d groups of wildcards. The new index is particularly favorable for larger alphabets and comparable for smaller alphabets, such as DNA. A key to the space reduction is a result we give showing how any compressed suffix array can be supplemented with auxiliary data structures occupying O(n)+O(dlognd) bits to also support efficient dictionary matching queries. We discuss how the space can be reduced further by a number of approaches and by allowing an increase in the worst case query time. We also present a new query algorithm for our wildcard indexes that can greatly reduce the query working space. © 2012 Elsevier B.V. All rights reserved.
Maurer D.,McMaster University |
Werker J.F.,University of British Columbia
Developmental Psychobiology | Year: 2014
In this article, we begin with a summary of the evidence for perceptual narrowing for various aspects of language (e.g., vowel and consonant contrasts, tone languages, visual language, sign language) and of faces (e.g., own species, own race). We then consider possible reasons for the apparent differences in the timing of narrowing (e.g., apparently earlier for own race than for own species). Throughout we consider whether the evidence fits a model of maintenance/loss or is better characterized as enhancement/attunement to exposed categories. Finally, we consider evidence on the malleability of the timing and its implications for the role of endogenous factors versus learning in controlling when narrowing occurs. Overall, the comparison across domains revealed many similarities but also striking differences which lead to suggestions for future research. © 2013 Wiley Periodicals, Inc.
Tzeng Y.-C.,University of Otago |
Ainslie P.N.,University of British Columbia
European Journal of Applied Physiology | Year: 2014
Cerebral autoregulation (CA) is integral to the delicate process of maintaining stable cerebral perfusion and brain tissue oxygenation against changes in arterial blood pressure. The last four decades has seen dramatic advances in understanding CA physiology, and the role that CA might play in the causation and progression of disease processes that affect the cerebral circulation such as stroke. However, the translation of these basic scientific advances into clinical practice has been limited by the maintenance of old constructs and because there are persistent gaps in our understanding of how this vital vascular mechanism should be quantified. In this review, we re-evaluate relevant studies that challenge established paradigms about how the cerebral perfusion pressure and blood flow are related. In the context of blood pressure being a major haemodynamic challenge to the cerebral circulation, we conclude that: (1) the physiological properties of CA remain inconclusive, (2) many extant methods for CA characterisation are based on simplistic assumptions that can give rise to misleading interpretations, and (3) robust evaluation of CA requires thorough consideration not only of active vasomotor function, but also the unique properties of the intracranial environment. © 2013 The Author(s).
Rachman S.,Kings College |
Rachman S.,University of British Columbia
Behaviour Research and Therapy | Year: 2012
The features of severe health anxiety, intense and persistent anxiety about one's present and future health, are described. In common with other anxiety disorders such as GAD, PTSD and OCD, the core of HAD is distressing, uncontrollable anxiety, and is classifiable as an Anxiety Disorder, Health Anxiety Disorder (HAD). The cognitive construal of HAD proposes that health anxiety is caused by catastrophic misinterpretations of the significance of sensations and/or changes in bodily functions and appearance (such as swellings, pain, loss of energy, dizzy spells). The nature, causes, triggers, persistence, assessment and treatment of HAD are reviewed, and the present status of the cognitive model is appraised. Suggestions are made for future research and clinical applications, and the need for incisive evaluations of the main premises of the model is emphasized. © 2012 Elsevier Ltd.
Hamann A.,University of Alberta |
Aitken S.N.,University of British Columbia
Diversity and Distributions | Year: 2013
Aim: A number of assumptions underpinning the use of species distribution models to predict biological responses to climate change are violated for temperate and boreal tree species that are widespread, long-lived and genetically adapted to local climate conditions. To address this situation, we propose a methodology to account for the potential effects of genetic structure, adaptive potential and limited migration capacity. Location: British Columbia, Canada. Methods: Similar to the widely used 'no migration' and 'unlimited migration' scenarios, we employ more refined biological response scenarios to evaluate the potential effects of genetic adaptation to local environments and the capacity of species to adapt and migrate. These scenarios are realized by two sets of geographic delineations that partition the species range into multiple populations and that subdivide the study area into smaller landscape units. Results: In a case study for British Columbia, we demonstrate how the approach can be used to evaluate the adequacy of a reserve system of 906 protected areas to ensure long-term maintenance of forest genetic resources for 48 tree species. We find that between 35% and 85% of locally adapted populations in protected areas are maintained under a median climate change scenario until the end of the century. A sensitivity analysis shows that assumptions about migration and adaptation capacity of species have a major effect on the projected conservation status. Main conclusions: We propose that the results of species distribution models have practical value for conservation planning if the focus is on maintenance rather than loss of suitable habitat. Accounting for genetic structure, adaptive potential and migration capacity through best-case and worst-case scenarios provide important information to effectively allocate limited resources available for conservation action. © 2012 Blackwell Publishing Ltd.
Agrawal A.F.,University of Toronto |
Whitlock M.C.,University of British Columbia
Genetics | Year: 2011
Data from several thousand knockout mutations in yeast (Saccharomyces cerevisiae) were used to estimate the distribution of dominance coefficients. We propose a new unbiased likelihood approach to measuring dominance coefficients. On average, deleterious mutations are partially recessive, with a mean dominance coefficient ∼0.2. Alleles with large homozygous effects are more likely to be more recessive than are alleles of weaker effect. Our approach allows us to quantify, for the first time, the substantial variance and skew in the distribution of dominance coefficients. This heterogeneity is so great that many population genetic processes analyses based on the mean dominance coefficient alone will be in substantial error. These results are applied to the debate about various mechanisms for the evolution of dominance, and we conclude that they are most consistent with models that depend on indirect selection on homeostatic gene expression or on the ability to perform well under periods of high demand for a protein. Copyright © 2011 by the Genetics Society of America.
Wiebe N.J.,University of British Columbia
PLoS computational biology | Year: 2010
The prediction of functional RNA structures has attracted increased interest, as it allows us to study the potential functional roles of many genes. RNA structure prediction methods, however, assume that there is a unique functional RNA structure and also do not predict functional features required for in vivo folding. In order to understand how functional RNA structures form in vivo, we require sophisticated experiments or reliable prediction methods. So far, there exist only a few, experimentally validated transient RNA structures. On the computational side, there exist several computer programs which aim to predict the co-transcriptional folding pathway in vivo, but these make a range of simplifying assumptions and do not capture all features known to influence RNA folding in vivo. We want to investigate if evolutionarily related RNA genes fold in a similar way in vivo. To this end, we have developed a new computational method, Transat, which detects conserved helices of high statistical significance. We introduce the method, present a comprehensive performance evaluation and show that Transat is able to predict the structural features of known reference structures including pseudo-knotted ones as well as those of known alternative structural configurations. Transat can also identify unstructured sub-sequences bound by other molecules and provides evidence for new helices which may define folding pathways, supporting the notion that homologous RNA sequence not only assume a similar reference RNA structure, but also fold similarly. Finally, we show that the structural features predicted by Transat differ from those assuming thermodynamic equilibrium. Unlike the existing methods for predicting folding pathways, our method works in a comparative way. This has the disadvantage of not being able to predict features as function of time, but has the considerable advantage of highlighting conserved features and of not requiring a detailed knowledge of the cellular environment.
Rajcan-Separovic E.,University of British Columbia
Human Reproduction Update | Year: 2012
Background: Chromosome microarray (CMA) testing allows automatic and easy identification of large chromosomal abnormalities detectable by conventional cytogenetics as well as the detection of submicroscopic chromosomal imbalances. Methods: A PubMed search was performed in order to review the current use of CMA testing in the field of human reproduction. Articles discussing the use of CMA in the preimplantation setting, ongoing pregnancies, miscarriages and patients with reproductive disorders were considered. Results: A high rate of concordance between conventional methods of detecting chromosomal abnormalities [e.g. fluorescence in situ hybridization (FISH), karyotyping] and CMA was reported in the prenatal setting with CMA providing more comprehensive and detailed results as it investigates the whole genome at higher resolution. In preimplantation genetic screening, CMA is replacing FISH and the selection of embryos based on CMA has already resulted in live births. For ongoing pregnancies and miscarriages, CMA eliminates tissue culture failures and artifacts and allows a quick turnaround time. The detection of submicroscopic imbalances [or copy number variants (CNVs)] is beneficial when the imbalance has a clear clinical consequence but is challenging for previously undescribed imbalances, particularly for ongoing pregnancies. Recurrent CNVs have been documented in patients with reproductive disorders; however, the application of CMA in this field is still limited. Conclusions: CMA enhances reproductive medicine as it facilitates better understanding of the genetic aspects of human development and reproduction and more informed patient management. Further clinical validation of CMA in the prenatal setting, creation of practice guidelines and catalogs of newly discovered submicroscopic imbalances with clinical outcomes are areas that will require attention in the future. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Ward M.H.,University of British Columbia
Physics of Fluids | Year: 2011
Two superposed thin layers of fluids are prone to interfacial instabilities due to London-van der Waals forces. Evolution equations for the film thicknesses are derived using lubrication theory. Using the intrinsic scales, for a single layer, results in a system with parametric dependence of four ratios of the two layers: surface tension, Hamaker constant, viscosity, and film thickness. In contrast to the single layer case, the bilayer system has two unstable eigenmodes: squeezing and bending. For some particular parameter regimes, the system exhibits the avoided crossing behavior, where the two eigenmodes are interchanged. Based on numerical analysis, the system evolves into four different rupture states: basal layer rupture, upper layer rupture, double layer rupture, and mixed layer rupture. The ratio of Hamaker constants and the relative film thickness of the two layers control the system dynamics. Remarkably, the line of avoided crossing demarks the transition region of mode mixing and energy transfer, affecting the scaling of the dynamical regime map consequentially. Asymptotic and numerical analyses are used to examine the self-similar ruptures and to extract the power law scalings for both the basal layer rupture and the upper layer rupture. The scaling laws for the basal layer rupture are the same as those of the single layer on top of a substrate. The scaling laws for the upper layer rupture are different: the lateral length scale decreases according to (tr-t)1/3 and the film thickness decreases according to (tr-t)1/6. © 2011 American Institute of Physics.
Floresco S.B.,University of British Columbia
Trends in Neurosciences | Year: 2015
Varazzani and colleagues explored how noradrenergic and dopaminergic neural activity relates to cost/benefit decisions involving effort. They show these systems may play complementary roles in resolving these decisions; dopamine encodes cost-discounted values of rewards, whereas noradrenergic cells modify activity in relation to the amount of effort required to obtain them. © 2015 Elsevier Ltd.
Lam R.W.,University of British Columbia
Journal of psychopharmacology (Oxford, England) | Year: 2010
Antidepressants were traditionally considered to have delayed onset of action, and clinical opinion often stated that patients may not experience noticeable improvement for 4-6 weeks. Recent studies have shown, however, that antidepressants have more rapid onset of effect, within 1-2 weeks, and that this early response may be associated with later sustained response. Moreover, there is emerging evidence that some medications may have faster onset of therapeutic effect than others. The new antidepressant agomelatine, with its novel pharmacological profile as an agonist at melatonergic (MT(1) and MT(2)) receptors and antagonist at 5-HT(2C) receptors, has in several studies produced earlier symptom improvement than comparator selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors. In particular, beneficial effects on sleep and daytime functioning are noticeable as early as the first week of treatment. These therapeutic benefits may, in part, be related to its regulatory effects on circadian and sleep- wake cycles. Agomelatine therefore combines early symptom relief with a favorable side-effect profile and short-term and long-term antidepressant efficacy. These properties suggest that agomelatine can be considered a first-line treatment for patients with major depression.
Stamp P.C.E.,University of British Columbia
New Journal of Physics | Year: 2015
It is argued that gravity should cause a breakdown of quantum mechanics, at low energies, accessible to table-top experiments. It is then shown that one can formulate a theory of quantum gravity in which gravitational correlations exist between worldline or worldsheet paths, for the particle or field of interest. Using a generalized equivalence principle, one can give a unique form for the correlators, yielding a theory with no adjustable parameters. A key feature of the theory is the 'bunching' of quantum trajectories caused by the gravitational correlations - this is not a decoherence or a 'collapse' mechanism. This bunching causes a breakdown of the superposition principle for large masses, with a very rapid crossover to classical behaviour at an energy scale which depends on the physical structure of the object. Formal details, and applications of the theory, are kept to a minimum in this paper; but we show how physical quantities can be calculated, and give a detailed discussion of the dynamics of a single particle. © 2015 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.
Urban F.R.,University of British Columbia
Journal of Cosmology and Astroparticle Physics | Year: 2011
We investigate in more depth the issue of backreaction in models that attempt at generating cosmological magnetic fields at inflation. By choosing different, physically motivated, parametrisations, we are able to isolate the heart of the problem, namely the existence, alongside the wanted magnetic field, of its electric counterpart, which turns out quite generally to be stronger and redder. We were also able to identify a few more interwoven weak spots (the typically very high scale of inflation, the width of the spectrum of modes processed by inflation, the blindness of the amplification mechanism to the energy scale processed), in a way independent on the specifications of the coupling between inflation and electromagnetism. Despite having stripped down the problem to the core, the obstacles encountered appear insurmountable, thereby posing a challenge to inflation as the incubator of cosmological magnetism. ©2011 IOP Publishing Ltd and SISSA.
Freeman H.J.,University of British Columbia
Canadian Journal of Gastroenterology | Year: 2013
BACKGROUND: Serological studies suggest that celiac disease may be present in approximately 0.5% to 1% of the North American population. Screening data based on small intestinal biopsy performed during routine endoscopic evaluations are not available. METHODS: Patients referred between January 1982 and December 2011 for evaluation of gastrointestinal symptoms and requiring elective investigative upper endoscopic evaluation underwent duodenal biopsies to determine whether changes of adult celiac disease were present. RESULTS: A total of 9665 patients, including 4008 (41.5%) males and 5657 (68.5%) females, underwent elective endoscopies and duodenal biopsies. Of these, 234 (2.4%) exhibited changes of celiac disease including 73 males (1.8%) and 161 females (2.8%). During the first 20 years, the number of biopsy-positive patients in five-year intervals progressively decreased and, subsequently, during the next 10 years, the number progressively increased. CONCLUSIONS: Celiac disease is far more common in specialist practice than has been suggested in the evaluation of healthy populations using serological screening studies. Endoscopic duodenal biopsy is an important method of identifying underlying celiac disease and should be routinely considered in all patients undergoing an elective endoscopic evaluation. Noninherited factors, possibly environmental, may play a role in the appearance of biopsy-defined celiac disease and alter detection over time. ©2013 Pulsus Group Inc. All rights reserved.
Donner S.D.,University of British Columbia
Climatic Change | Year: 2014
The late founder of this journal, Stephen Schneider, argued that climate scientists must find the right balance between being honest about the limits of our knowledge and being effective in communicating the risks that climate change poses to society. The worlds of science and communications have changed dramatically in the years since Schneider first described this "double ethical bind". Yet for most scientists, the core challenge of public communication remains. How do we choose between what we perceive as science - being honest - and what we perceive as advocacy - being effective? This essay suggests that scientists should view science and advocacy as opposite ends of a continuum with many possible positions. Drawing upon findings from psychology, communications, and science and technology studies, I describe how scientists can use research and critical self-analysis to be "scientific" about public engagement and to choose a suitable place for themselves on the science-advocacy continuum. © 2014 Springer Science+Business Media Dordrecht.
Christen A.,University of British Columbia
Urban Climate | Year: 2014
There is growing interest to constrain and validate greenhouse gas (GHG) emission inventories at urban and intra-urban scales. This contribution reviews methods to identify, quantify and attribute emissions (and sequestration) of carbon dioxide, methane and nitrous oxide in cities using in-situ measurements in the atmosphere. Measurements of GHG mixing ratios and fluxes in cities will allow validation of inventories, identification and quantification of poorly-known sources and accounting for the effects of urban land-cover change. In-situ measurements of GHG emissions (and sequestration) in the urban atmosphere are possible (i) at the micro-scale by capturing GHG plumes of individual sources using mobile platforms and measuring vertical profiles of GHGs in the urban canopy layer, (ii) at the local-scale by direct eddy-covariance flux measurements of GHGs on towers, and, (iii) at the meso-scale by measurements of mixing ratios and isotopologues of GHGs in the urban and rural boundary layer combined with box and inverse models. This paper reviews all approaches and highlights their potential and current limitations. These observational methods combined with models will support future endeavors in fine-scale GHG emission monitoring in cities and allow for validation of upcoming remote-sensing products of urban-scale GHG emissions. © 2014 Elsevier B.V.
Louis-Martinez D.J.,University of British Columbia
Classical and Quantum Gravity | Year: 2011
A classical (non-quantum-mechanical) relativistic ideal gas in thermodynamic equilibrium in a uniformly accelerated frame of reference is studied using Gibbs's microcanonical and grand canonical formulations of statistical mechanics. Using these methods explicit expressions for the particle, energy and entropy density distributions are obtained, which are found to be in agreement with the well-known results of the relativistic formulation of Boltzmann's kinetic theory. Explicit expressions for the total entropy, total energy and rest mass of the gas are obtained. The position of the center of mass of the gas in equilibrium is found. The non-relativistic and ultrarelativistic approximations are also considered. The phase space volume of the system is calculated explicitly in the ultrarelativistic approximation. © 2011 IOP Publishing Ltd.
Zhitnitsky A.R.,University of British Columbia
Nuclear Physics A | Year: 2011
The violation of local P and CP invariance in QCD has been a subject of intense discussions for the last couple of years as a result of very interesting ongoing results coming from RHIC. Separately, a new thermalization scenario for heavy ion collisions through the event horizon as a manifestation of the Unruh effect, has been also suggested. In this paper we argue that these two, naively unrelated phenomena, are actually two sides of the same coin as they are deeply rooted into the same fundamental physics related to some very nontrivial topological features of QCD. We formulate the universality conjecture for P and CP odd effects in heavy ion collisions analogous to the universal thermal behaviour observed in all other high energy interactions. © 2011 Elsevier B.V.
Strasburg J.L.,Indiana University |
Rieseberg L.H.,Indiana University |
Rieseberg L.H.,University of British Columbia
Molecular Biology and Evolution | Year: 2010
Methods developed over the past decade have made it possible to estimate molecular demographic parameters such as effective population size, divergence time, and gene flow with unprecedented accuracy and precision. However, they make simplifying assumptions about certain aspects of the species' histories and the nature of the genetic data, and it is not clear how robust they are to violations of these assumptions. Here, we use simulated data sets to examine the effects of a number of violations of the "Isolation with Migration" (IM) model, including intralocus recombination, population structure, gene flow from an unsampled species, linkage among loci, and divergent selection, on demographic parameter estimates made using the program IMA. We also examine the effect of having data that fit a nucleotide substitution model other than the two relatively simple models available in IMA. We find that IMA estimates are generally quite robust to small to moderate violations of the IM model assumptions, comparable with what is often encountered in real-world scenarios. In particular, population structure within species, a condition encountered to some degree in virtually all species, has little effect on parameter estimates even for fairly high levels of structure. Likewise, most parameter estimates are robust to significant levels of recombination when data sets are pared down to apparently nonrecombining blocks, although substantial bias is introduced to several estimates when the entire data set with recombination is included. In contrast, a poor fit to the nucleotide substitution model can result in an increased error rate, in some cases due to a predictable bias and in other cases due to an increase in variance in parameter estimates among data sets simulated under the same conditions.
Elfring G.J.,University of British Columbia
Physics of Fluids | Year: 2015
The use of the reciprocal theorem has been shown to be a powerful tool to obtain the swimming velocity of bodies at low Reynolds number. The use of this method for lower-dimensional swimmers, such as cylinders and sheets, is more problematic because of the undefined or ill-posed resistance problems that arise in the rigid-body translation of these shapes. Here, we show that this issue can be simply circumvented and give concise formulas obtained via the reciprocal theorem for the self-propelled motion of deforming two-dimensional bodies. We also discuss the connection between these formulae and Faxén's laws. © 2015 AIP Publishing LLC.
Poole G.,University of British Columbia
Current HIV Research | Year: 2012
There is a pressing need to find an efficacious HIV vaccine and a concomitant need for the recruitment of participants in efficacy trials. These efforts are hampered, however, by a gap between what respondents say they will do regarding research participation, and whether they actually enroll. The current paper examines the size of this gap and proposes psychological reasons for it. Some reasons include the temporal stability of the intention, the time taken to consider its ramifications and plans to deal with them, and the social forces that affect the intention. From this analysis, recommendations are offered to improve recruitment efforts and the predictive power of expressions of willingness to participate. © 2012 Bentham Science Publishers.
Kuttner L.,University of British Columbia
Paediatric Anaesthesia | Year: 2012
Objective: Pediatric hypnosis has a useful role in pre-, peri-, and post-anesthesia to minimize anticipatory anxiety, and as adjunctive treatment to reduce and control pain. This article reviews the literature in the use of hypnosis in pediatric anesthesia to highlight its role and relevancy. Background: Current research indicates there is an immediate and enduring impact, and long-term benefits of this child-centered intervention. Hypnosis can be included in presurgical consultations to establish cooperation and signals for increasing comfort and to address fears and provide suggestions for rapid recovery with changed expectations for the child's own benefit. Thus prepared, the child is in a heightened state of receptivity and statements and suggestions carry through to peri- and post-anesthesia, when hypnosis can help with extubation, reduce nausea, and ease recovery. Method: The Magic Glove is one hypno-anesthesia technique that simultaneously addresses pain and anxiety. The process of hypnosis requires training and supervised practice. Conclusion: Patients in hypnosis treatment conditions have less anxiety and shorter hospital stays and experience less long-term pain and discomfort than do patients in control conditions. There appears little reason not to provide hypnosis as an adjunctive treatment for pediatric patients undergoing anesthesia. © 2012 Blackwell Publishing Ltd.
Eisen A.,University of British Columbia |
Kuwabara S.,Chiba University
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2012
In amyotrophic lateral sclerosis (ALS), hand muscle wasting preferentially affects the 'thenar (lateral) hand', including the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles, with relative sparing of the hypothenar muscles (the abductor digiti minimi (ADM)). This peculiar pattern of dissociated atrophy of the intrinsic hand muscles is termed the 'split hand' and is rarely seen in diseases other than ALS. The muscles involved in the split hand are innervated through the same spinal segments (C8 and T1), and FDI and ADM, which are differentially affected, are both ulnar nerve innervated. The physiological mechanisms underlying the split hand in ALS are incompletely understood but both cortical and spinal/peripheral mechanisms are probably involved. Motor potentials evoked by magnetic stimulation are significantly smaller when recorded from the thenar complex, compared with the hypothenar muscles, supporting a cortical mechanism. But peripheral axonal excitability studies have suggested that APB/FDI motor axons have more prominent persistent sodium currents than ADM axons, leading to higher axonal excitability and thereby more ready degeneration. Pincer or precision grip is vital to human hand function, and frequent use of thenar complex muscles may lead to greater oxidative stress and metabolic demands at both upper and lower motoneurons innervating the APB and FDI. The split hand is a useful diagnostic sign in early ALS, and recent objective studies indicate that the sign has a high degree of specificity.
Benavente O.R.,University of British Columbia |
Hart R.G.,Population Health Research Institute |
McClure L.A.,University of Alabama at Birmingham |
Szychowski J.M.,University of Alabama at Birmingham |
Coffey C.S.,University of Iowa
New England Journal of Medicine | Year: 2012
BACKGROUND: Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. METHODS: We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. RESULTS: The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P = 0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone). CONCLUSIONS: Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.) Copyright © 2012 Massachusetts Medical Society. All rights reserved.
Andrade J.,Montreal Heart Institute |
Andrade J.,University of British Columbia |
Khairy P.,Montreal Heart Institute |
Dobrev D.,University of Duisburg - Essen |
Nattel S.,Montreal Heart Institute
Circulation Research | Year: 2014
Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management. © 2014 American Heart Association, Inc.
Agrawal A.F.,University of Toronto |
Whitlock M.C.,University of British Columbia
Trends in Ecology and Evolution | Year: 2010
To an evolutionary geneticist, the most important property of a new mutation is its effect on fitness. Stress is a reduction in fitness that can also alter the selection on new mutations. Although the effects of environmental and genetic stresses are typically studied separately, it is useful to consider them from the same perspective. Here we evaluate the common perception that stress increases selection. We consider various conceptual paradigms for thinking about selection and stress, and then review the empirical data. We reject the notion that stress typically increases selection. Instead, we find that different types of stresses affect selection differently, though the underlying mechanisms are, as yet, unclear in most cases. © 2010 Elsevier Ltd.
Hopcraft J.G.C.,University of Groningen |
Olff H.,University of Groningen |
Sinclair A.R.E.,University of British Columbia
Trends in Ecology and Evolution | Year: 2010
Herbivores are regulated by predation under certain environmental conditions, whereas under others they are limited by forage abundance and nutritional quality. Whether top-down or bottom-up regulation prevails depends both on abiotic constraints on forage availability and body size, because size simultaneously affects the risk of predation of herbivores and their nutritional demands. Consequently, ecosystems composed of similar species can have different dynamics if they differ in resource supply. Here, we use large herbivore assemblages in African savanna ecosystems to develop a framework that connects environmental gradients and disturbance patterns with body size and trophic structure. This framework provides a model for understanding the functioning and diversity of ecosystems in general, and unifies how top-down and bottom-up mechanisms depend on common underlying environmental gradients. © 2009 Elsevier Ltd. All rights reserved.
Barrett R.D.H.,University of British Columbia
Journal of Fish Biology | Year: 2010
The three-spined stickleback Gasterosteus aculeatus is a model species for studying questions in ecology and evolution. The rapid diversification of G. aculeatus in post-glacial freshwater environments, combined with recently developed molecular tools, provides a unique opportunity to study the functional basis of fitness variation in natural populations. In derived freshwater populations, a number of morphological traits have diverged in parallel from the marine ancestral state, including the number of lateral armour plates. Evolution of reduced armour in freshwater populations is due to positive selection from both abiotic and biotic mechanisms. The major effect gene (ectodysplasin-A or Eda), along with several minor effect genetic regions, has recently been shown to control lateral plate variation. Field experiments have further determined the fitness consequences of allelic variation at the major effect locus. This work helps elucidate the mechanisms connecting genetic variation with phenotypic variation and fitness in the wild, a synthesis that should be applicable to many other phenotypic traits and species of fishes. © 2010 The Author. Journal compilation © 2010 The Fisheries Society of the British Isles.
Madden K.M.,University of British Columbia
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy | Year: 2013
Exercise interventions are recommended in most guidelines for the treatment of type 2 diabetes. Although most guidelines suggest a combination of both aerobic and resistance training, the exact benefits of these interventions remain unclear. Although either modality alone or in combination seems to have an identical impact on glycated hemoglobin levels, resistance training and aerobic training have independent effects on other parameters of cardio-metabolic risk. This review examines the current evidence for aerobic and resistance training on glycemic control, lipid profile, body composition, vascular health, and mental health in patients with type 2 diabetes. The uncertainties surrounding exercise modality, volume and intensity are also addressed. © 2013 Madden, publisher and licensee Dove Medical Press Ltd.
Tanner M.E.,University of British Columbia
Natural Product Reports | Year: 2015
Prenylated indole alkaloids comprise a large and structurally diverse family of natural products that often display potent biological activities. In recent years a large family of prenyltransferases that install prenyl groups onto the indole core have been discovered. While the vast majority of these enzymes are evolutionarily related and share a common protein fold, they are remarkably versatile in their ability to catalyze reverse and normal prenylations at all positions on the indole ring. This highlight article will focus on recent studies of the mechanisms utilized by indole prenyltransferases. While all of the prenylation reactions may follow a direct electrophilic aromatic substitution mechanism, studies of structure and reactivity suggest that in some cases prenylation may first occur at the nucleophilic C-3 position, and subsequent rearrangements then generate the final product. © 2014 The Royal Society of Chemistry.
Walley K.R.,University of British Columbia
Current Infectious Disease Reports | Year: 2013
There is much enthusiasm and interest in sepsis biomarkers, particularly because sepsis is a highly lethal condition, its diagnosis is challenging, and even simple treatment with antibiotics has led to serious adverse consequences such as emergence of resistant pathogens. Yet development of a sepsis biomarker requires many more steps than simply finding an association between a particular molecule and a clinical state or outcome. Demonstration of improvement of therapeutic practice using receiver-operating characteristic and other analyses is important. Validation in independent, prospective and, preferably, multicenter trials is essential. Many promising candidate sepsis biomarkers have recently been proposed. While procalcitonin (PCT) is currently the most studied sepsis biomarker, evidence of potential value has been found for a wide array of blood biomarkers including proteins, mRNA expression in whole blood or leukocytes, micro-RNAs (miRNA), pathogen and host DNA, pathogen and host genetic variants and metabolomic panels, and even in the novel use of currently available clinical data. While the most common early reports link putative sepsis biomarker levels to severity of illness and outcome (prognostic), this is not anticipated to be their primary use. More important is the distinction between infection and noninfectious inflammatory responses (diagnostic) and the use of sepsis biomarkers to direct therapy (predictive). © 2013 Springer Science+Business Media New York.
Peirce A.,University of British Columbia
Computer Methods in Applied Mechanics and Engineering | Year: 2010
We describe a novel cubic Hermite collocation scheme for the solution of the coupled integro-partial differential equations governing the propagation of a hydraulic fracture in a state of plane strain. Special blended cubic Hermite-power-law basis functions, with arbitrary index 0<1, are developed to treat the singular behavior of the solution that typically occurs at the tips of a hydraulic fracture. The implementation of blended infinite elements to model semi-infinite crack problems is also described. Explicit formulae for the integrated kernels associated with the cubic Hermite and blended basis functions are provided. The cubic Hermite collocation algorithm is used to solve a number of different test problems with two distinct propagation regimes and the results are shown to converge to published similarity and asymptotic solutions. The convergence rate of the cubic Hermite scheme is determined by the order of accuracy of the tip asymptotic expansion as well as the O(h4) error due to the Hermite cubic interpolation. The errors due to these two approximations need to be matched in order to achieve optimal convergence. Backward Euler time-stepping yields a robust algorithm that, along with geometric increments in the time-step, can be used to explore the transition between propagation regimes over many orders of magnitude in time. © 2010 Elsevier B.V.
Gregory D.,University of British Columbia
Geographical Journal | Year: 2011
Much of the discussion of 9/11 has debated its historical significance, but it is equally important to explore the geographical dimensions of the wars that have been conducted in its shadows. Subsequent transformations in the American way of war have played a major role in the increased militarisation of the planet. Most attention has been focused on Afghanistan and Iraq as the principal theatres of the 'war on terror', but one of the characteristics of late modern war is the emergent, 'event-ful' quality of military, paramilitary and terrorist violence that can, in principle, occur anywhere. Vulnerabilities are differentially distributed but widely dispersed, and in consequence late modern war is being changed by the slippery spaces through which it is conducted. This paper explores three global borderlands to bring those changes into focus: Afghanistan-Pakistan (particularly the deployment of CIA-controlled drones in Pakistan), US-Mexico (particularly the expansion of Mexico's 'drug war' and the US militarisation of the border), and cyberspace (particularly the role of stealth attacks on critical infrastructure and the formation of US Cyber Command). © 2011 The Author. The Geographical Journal © 2011 Royal Geographical Society (with the Institute of British Geographers).
Elliott S.R.,Los Alamos National Laboratory |
Franz M.,University of British Columbia
Reviews of Modern Physics | Year: 2015
Ettore Majorana (1906-1938) disappeared while traveling by ship from Palermo to Naples in 1938. His fate has never been fully resolved and several articles have been written that explore the mystery itself. His demise intrigues us still today because of his seminal work, published the previous year, that established symmetric solutions to the Dirac equation that describe a fermionic particle that is its own antiparticle. This work has long had a significant impact in neutrino physics, where this fundamental question regarding the particle remains unanswered. But the formalism he developed has found many uses as there are now a number of candidate spin-1/2 neutral particles that may be truly neutral with no quantum number to distinguish them from their antiparticles. If such particles exist, they will influence many areas of nuclear and particle physics. Most notably the process of neutrinoless double beta decay can exist only if neutrinos are massive Majorana particles. Hence, many efforts to search for this process are underway. Majorana's influence does not stop with particle physics, however, even though that was his original consideration. The equations he derived also arise in solid-state physics where they describe electronic states in materials with superconducting order. Of special interest here is the class of solutions of the Majorana equation in one and two spatial dimensions at exactly zero energy. These Majorana zero modes are endowed with some remarkable physical properties that may lead to advances in quantum computing and, in fact, there is evidence that they have been experimentally observed. This Colloquium first summarizes the basics of Majorana's theory and its implications. It then provides an overview of the rich experimental programs trying to find a fermion that is its own antiparticle in nuclear, particle, and solid-state physics. © 2015 American Physical Society.
Keeling P.J.,University of British Columbia
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010
Plastids and mitochondria each arose from a single endosymbiotic event and share many similarities in how they were reduced and integrated with their host. However, the subsequent evolution of the two organelles could hardly be more different: mitochondria are a stable fixture of eukaryotic cells that are neither lost nor shuffled between lineages, whereas plastid evolution has been a complex mix of movement, loss and replacement. Molecular data from the past decade have substantially untangled this complex history, and we now know that plastids are derived from a single endosymbiotic event in the ancestor of glaucophytes, red algae and green algae (including plants). The plastids of both red algae and green algae were subsequently transferred to other lineages by secondary endosymbiosis. Green algal plastids were taken up by euglenids and chlorarachniophytes, as well as one small group of dinoflagellates. Red algae appear to have been taken up only once, giving rise to a diverse group called chromalveolates. Additional layers of complexity come from plastid loss, which has happened at least once and probably many times, and replacement. Plastid loss is difficult to prove, and cryptic, non-photosynthetic plastids are being found in many non-photosynthetic lineages. In other cases, photosynthetic lineages are now understood to have evolved from ancestors with a plastid of different origin, so an ancestral plastid has been replaced with a new one. Such replacement has taken place in several dinoflagellates (by tertiary endosymbiosis with other chromalveolates or serial secondary endosymbiosis with a green alga), and apparently also in two rhizarian lineages: chlorarachniophytes and Paulinella (which appear to have evolved from chromalveolate ancestors). The many twists and turns of plastid evolution each represent major evolutionary transitions, and each offers a glimpse into how genomes evolve and how cells integrate through gene transfers and protein trafficking. © 2010 The Royal Society.
Andreasson E.,Lund University |
Andreasson E.,Swedish University of Agricultural Sciences |
Ellis B.,University of British Columbia
Trends in Plant Science | Year: 2010
Although mitogen-activated protein kinase (MAPK) signal transduction cascades are known regulators of various aspects of plant biology, our knowledge of these systems has been largely restricted to a small subset of the MAPKs. However, global analyses are now revealing that many more of these kinases are probably engaged in modulating developmental and fitness adaptation processes in the plant kingdom. In this review, we show how these new findings are beginning to define the overall architecture of plant MAPK signaling, with a particular focus on the interplay between the terminal MPKs and their activators, inactivators and cellular targets. © 2009 Elsevier Ltd. All rights reserved.
Nosil P.,University of Colorado at Boulder |
Nosil P.,Institute for Advanced Study |
Schluter D.,University of British Columbia
Trends in Ecology and Evolution | Year: 2011
The long-standing goal of finding genes causing reproductive isolation is being achieved. To better link the genetics with the process of speciation, we propose that 'speciation gene' be defined as any gene contributing to the evolution of reproductive isolation. Characterizing a speciation gene involves establishing that the gene affects a component of reproductive isolation; demonstrating that divergence at the locus occurred before completion of speciation; and quantifying the effect size of the gene (i.e. the increase in total reproductive isolation caused by its divergence). Review of a sample of candidate speciation genes found that few meet these criteria. Improved characterization of speciation genes will clarify how numerous they are, their properties and how they affect genome-wide patterns of divergence. © 2011 Elsevier Ltd.
Walsh Z.,University of British Columbia
Law and Human Behavior | Year: 2013
This study aimed to determine the cross-ethnic stability of the predictive relationship of psychopathy for violence. Participants were 424 adult male jail inmates. Psychopathy was assessed using the Psychopathy Checklist-Revised and criminal violence was assessed using a comprehensive database of arrests for violent crimes. Ethnic categories included the groups that make up the vast majority of US inmates: European American (EA, n = 166), African American (AA, n = 174), and Latino American (LA, n = 84). Ethnically aggregated Cox regression survival analyses identified predictive effects for psychopathy. Disaggregated analyses identified ethnic differences: Psychopathy was more strongly predictive of violence among EA (R2 =.13, 95% CI [.04,.22], p <.01) relative to AA inmates (R2 =.05, 95% CI [.00,.11], p <.01) and was not related to violence among LA participants (R2=.02, 95% CI [.00,.08], p =.22). Receiver operating characteristic curve analyses yielded an equivalent pattern of results. These findings add to a growing literature suggesting cross-ethnic variability in the predictive power of psychopathy for violence. (PsycINFO Database Record (c) 2013 American Psychological Association. © 2012 American Psychological Association.
Maciejewski W.,University of British Columbia
Journal of Theoretical Biology | Year: 2014
Evolutionary graph theory has grown to be an area of intense study. Despite the amount of interest in the field, it seems to have grown separate from other subfields of population genetics and evolution. In the current work I introduce the concept of Fisher's (1930) reproductive value into the study of evolution on graphs. Reproductive value is a measure of the expected genetic contribution of an individual to a distant future generation. In a heterogeneous graph-structured population, differences in the number of connections among individuals translate into differences in the expected number of offspring, even if all individuals have the same fecundity. These differences are accounted for by reproductive value. The introduction of reproductive value permits the calculation of the fixation probability of a mutant in a neutral evolutionary process in any graph-structured population for either the moran birth-death or death-birth process. © 2013 Elsevier Ltd.
Davies-Thompson J.,University of British Columbia
Neuropsychologia | Year: 2013
Congenital achiasma offers a rare opportunity to study reorganization and inter-hemispheric communication in the face of anomalous inputs to striate cortex. We report neuroimaging studies of a patient with seesaw nystagmus, achiasma, and full visual fields. The subject underwent structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) studies, and functional MRI (fMRI) using monocular stimulation with checkerboards, motion, objects and faces, as well as retinotopic quadrantic mapping. Structural MRI confirmed the absence of an optic chiasm, which was corroborated by DTI tractography. Lack of a functioning decussation was confirmed by fMRI that showed activation of only ipsilateral medial occipital cortex by monocular stimulation. The corpus callosum was normal in size and anterior and posterior commissures were identifiable. In terms of the hierarchy of visual areas, V5 was the lowest level region to be activated binocularly, as were regions in the fusiform gyri responding to faces and objects. The retinotopic organization of striate cortex was studied with quadrantic stimulation. This showed that, in support of recent findings, rather than projecting to an ectopic location contiguous with the normal retinotopic map of the ipsilateral temporal hemi-retina, the nasal hemi-retina's representation overlapped that of the temporal hemi-retina. These findings show that congenital achiasma can be an isolated midline crossing defect, that information transfer does not occur in early occipital cortex but at intermediate and higher levels of the visual hierarchy, and that the functional reorganisation of striate cortex in this condition is consistent with normal axon guidance by a chemoaffinity gradient. Copyright © 2013 Elsevier Ltd. All rights reserved.
Walker L.J.,University of British Columbia
New Directions for Child and Adolescent Development | Year: 2013
What fundamentally motivates moral behavior? What is the nature and source of moral motivation? The argument developed in this chapter is that moral action is not merely other-regarding; it also can, and should be, self-regarding. When there is something significant for the self in the moral enterprise, it can legitimately be self-enhancing and, thus, powerfully motivating. The empirical warrant for this argument is found in the study of the psychological functioning of moral exemplars. The research reviewed here indicates that moral exemplars do synergistically integrate their self-promoting agentic motivation in service to their other-promoting communal values. Therein is the powerful motivational impetus for doing good and living rightly. © Wiley Periodicals, Inc.
Ross C.J.,University of British Columbia
Thyroid : official journal of the American Thyroid Association | Year: 2010
BACKGROUND: Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADRs and matched control patients. SUMMARY: ADRs represent a significant unmet medical problem with significant morbidity and mortality, and Canadian Pharmacogenomics Network for Drug Safety is a nation-wide network in Canada that seeks to identify genetic factors responsible for interindividual differences in susceptibility to serious ADRs. CONCLUSIONS: Active ADR surveillance is necessary to identify and recruit patients who suffer from serious ADRs. National and international collaborations are required to recruit sufficient patients for these studies. Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future.
Molday R.S.,University of British Columbia |
Kellner U.,MVZ ADTC Siegburg GmbH |
Weber B.H.F.,University of Regensburg
Progress in Retinal and Eye Research | Year: 2012
X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long-term retinoschisin expression and rescue of retinal structure and function providing a 'proof of concept' that gene therapy may be an effective treatment for XLRS. © 2012 Elsevier Ltd.
Maron J.L.,University of Montana |
Marler M.,University of Montana |
Klironomos J.N.,University of British Columbia |
Cleveland C.C.,University of Montana
Ecology Letters | Year: 2011
One robust result from many small-scale experiments has been that plant community productivity often increases with increasing plant diversity. Most frequently, resource-based or competitive interactions are thought to drive this positive diversity-productivity relationship. Here, we ask whether suppression of plant productivity by soil fungal pathogens might also drive a positive diversity-productivity relationship. We created plant assemblages that varied in diversity and crossed this with a ± soil fungicide treatment. In control (non-fungicide treated) assemblages there was a strong positive relationship between plant diversity and above-ground plant biomass. However, in fungicide-treated assemblages this relationship disappeared. This occurred because fungicide increased plant production by an average of 141% at the lower ends of diversity but boosted production by an average of only 33% at the higher ends of diversity, essentially flattening the diversity-productivity curve. These results suggest that soil pathogens might be a heretofore unappreciated driver of diversity-productivity relationships. © 2010 Blackwell Publishing Ltd/CNRS.
Hamilton T.,University of British Columbia
Skin therapy letter | Year: 2011
Cosmetics are an important cause of allergic contact dermatitis (ACD). Fragrances and preservatives are the two most clinically relevant allergens found in cosmetic products. Patch testing remains the gold standard for identification of causative allergens. Common cosmetic allergens are reviewed. Practical methods of allergen avoidance are also discussed.
Leitch H.A.,University of British Columbia
Drugs | Year: 2011
The myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of progression to acute myeloid leukaemia (AML). Most MDS patients eventually require transfusion of red blood cells for anaemia, placing them at risk of transfusional iron overload. In β-thalassaemia major, transfusional iron overload leads to organ dysfunction and death; however, with iron chelation therapy, organ function is improved, and survival improved to near normal and correlated with the degree of compliance with chelation. In lower-risk MDS, several nonrandomized studies suggest an adverse effect of iron overload on survival and that lowering iron with chelation may minimize this impact. Emerging data indicate that chelation may improve organ function, particularly hepatic function, and a minority of patients may have improvement in cell counts and decreased transfusion requirements. While guidelines for MDS generally recommend chelation in selected lower-risk patients, data from nonrandomized trials suggest iron overload may impact adversely on the outcome of higher-risk MDS and stem cell transplantation (SCT). This effect may be due to increased transplant-related mortality, infection and AML progression, and preliminary data suggest that lowering iron may be beneficial in this patient group. Other areas of active and future investigation include optimizing the monitoring of iron overload using imaging such as T2* MRI and measures of labile iron and oxidative stress; correlating new methods of measuring iron to clinical outcomes; clarifying the contribution of different cellular and extracellular iron pools to iron toxicity; optimizing chelation by using agents that access the appropriate iron pools to minimize the relevant clinical consequences in individual patients; and incorporating measures of quality of life and co-morbidities into clinical trials of chelation in MDS. It should be noted that chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available.In this review, data on the impact of iron overload in MDS and SCT are discussed; for example, several noncontrolled studies show inferior survival in patients with iron overload in these clinical settings, including an increase in transplant-related mortality and infection risk. Possible mechanisms of iron toxicity include oxidative stress, which can damage cellular components, and the documented impact of lowering iron on organ function with measures such as iron chelation therapy includes an improvement in elevated liver transaminases. Lowering iron also appears to improve survival in both lower-risk MDS and SCT in nonrandomized studies. Selected aspects of iron metabolism, transport, storage and distribution that may be amenable to future intervention and improved removal of iron from important cellular sites are discussed, as are attempts to quantify quality of life and the importance of co-morbidities in measures to treat MDS, including chelation therapy. © 2011 Adis Data Information BV. All rights reserved.
Trew J.L.,University of British Columbia
Clinical Psychology Review | Year: 2011
Human behavior can be organized around two fundamental motivational principles: the desire to approach positive outcomes and the desire to avoid negative outcomes. Both approach and avoidance motivation are relevant to a range of psychopathology, including depression. However, with some notable exceptions, avoidance processes have been underemphasized in the literature on motivational processes in depression. This review will examine the roles that approach and avoidance play in depression and will present an integrative model of approach and avoidance processes in depression. Both approach deficits and avoidance motivation are argued to play a role in limiting positive experiences and reinforcement for non-depressed behavior, contributing to the onset and maintenance of depression. In addition, avoidance processes are argued to play a role in negative information processing biases that may increase vulnerability to the onset and recurrence of depression. Lastly, avoidance processes and dysregulation in the connections between the approach and avoidance systems may contribute to depression by promoting inappropriate perseveration in the pursuit of unattainable approach goals. Theoretical rationales and empirical evidence for each of these roles are presented. Understanding the roles that both approach and avoidance play in depression may help to inform current conceptualizations of depression and improve treatment outcomes. © 2011 Elsevier Ltd.
Perrin D.M.,University of British Columbia
Accounts of Chemical Research | Year: 2016
ConspectusPositron emission tomography (PET) is revolutionizing our ability to visualize in vivo targets for target validation and personalized medicine. Of several classes of imaging agents, peptides afford high affinity and high specificity to distinguish pathologically distinct cell types by the presence of specific molecular targets. Of various available PET isotopes, [18F]-fluoride ion is preferred because of its excellent nuclear properties and on-demand production in hospitals at Curie levels. However, the short half-life of 18F and its lack of reactivity in water continue to challenge peptide labeling. Hence, peptides are often conjugated to a metal chelator for late-stage, one-step labeling. Yet radiometals, while effective, are neither as desirable nor as available as [18F]-fluoride ion. Despite considerable past success in identifying semifeasible radiosyntheses, significant challenges continue to confound tracer development. These interrelated challenges relate to (1) isotope/prosthetic choice; (2) bioconjugation for high affinity; (3) high radiochemical yields, (4) specific activities of >1 Ci/μmol to meet FDA microdose requirements; and (5) rapid clearance and in vivo stability. These enduring challenges have been extensively highlighted, while a single-step, operationally simple, and generally applicable means of labeling a peptide with [18F]-fluoride ion in good yield and high specific activity has eluded radiochemists and nuclear medicine practitioners for decades.Radiosynthetic ease is of primordial importance since multistep labeling reactions challenge clinical tracer production. In the past decade, as we sought to meet this challenge, appreciation of reactions with aqueous fluoride led us to consider organotrifluoroborate (RBF3 -) synthesis as a means of rapid aqueous peptide labeling. We have applied principles of mechanistic chemistry, knowledge of chemical reactivity, and synthetic chemistry to design stable RBF3 -s. Over the past 10 years, we have developed several new [18F]-RBF3 - radioprosthetic groups, all of which guarantee radiosynthetic ease while in most cases providing high tumor:nontumor (T:NT) ratios and moderate-to-high tumor uptake. Although others have developed methods for labeling of peptides with [18F]-silylfluorides or [18F]-Al-NOTA chelates, this Account focuses on the synthesis of [18F]-organotrifluoroborates.In this Account, I detail mechanistic, kinetic, thermodynamic, synthetic, and radiosynthetic approaches that enabled the translation of fundamental principles regarding the chemistry of RBF3 -s into a tantalizingly close realization of a clinical application of an [18F]-organotrifluoroborate-peptide conjugate for imaging of neuroendocrine tumors and the generalization of this method for labeling of several other peptides. © 2016 American Chemical Society.
Harley C.D.,University of British Columbia
Annals of the New York Academy of Sciences | Year: 2013
To predict community-level responses to climate change, we must understand how variation in environmental conditions drives changes in an organism's ability to acquire resources and translate those resources into growth, reproduction, and survival. This challenge can be approached mechanistically by establishing linkages from biophysics to community ecology. For example, body temperature can be predicted from environmental conditions and species-specific morphological and behavioral traits. Variation in body temperature within and among species dictates physiological performance, rates of resource acquisition, and growth. These ecological characteristics, along with population size, define the strength with which species interact. Finally, the direct (individual level) and indirect (community level) effects of temperature jointly determine community structure. This mechanistic framework can complement correlational approaches to better predict ecological responses to climate change and identify which characteristics of a species or community act as leverage points for change. Research priorities for further development of the mechanistic approach include documentation and prediction of relevant spatial and temporal variation in body temperature and the relationships between body temperature, individual performance, and interspecific interactions. © 2013 New York Academy of Sciences.
Taheri Najafabadi A.,University of British Columbia
International Journal of Energy Research | Year: 2013
In the fossil-fuel-based economies, current remedies for the CO2 reduction from large-scale energy consumers (e.g. power stations and cement works) mainly rely on carbon capture and storage, having three proposed generic solutions: post-combustion capture, pre-combustion capture, and oxy fuel combustion. All the aforementioned approaches are based on various physical and chemical phenomena including absorption, adsorption, and cryogenic capture of CO2. The purified carbon dioxide is sent for the physical storage options afterwards, using the earth as a gigantic reservoir with unknown long-term environmental impacts as well as possible hazards associated with that. Consequently, the ultimate solution for the CO2 sequestration is the chemical transformation of this stable molecule to useful products such as fuels (through, for example, Fischer-Tropsch chemistry) or polymers (through successive copolymerization and chain growth). This sustainably reduces carbon emissions, taking full advantage of CO2-derived chemical commodities, so-called carbon capture and conversion. Nevertheless, the surface chemistry of CO2 reduction is a challenge due to the presence of large energy barriers, requiring noticeable catalysis. This work aims to review the most recent advances in this concept selectively (CO2 conversion to fuels and CO2 copolymerization) with chemical engineering approach in terms of both materials and process design. Some of the most promising studies are expanded in detail, concluding with the necessity of subsidizing more research on CO2 conversion technologies considering the growing global concerns on carbon management. © 2013 John Wiley & Sons, Ltd.
Veen T.,University of British Columbia
Molecular Ecology | Year: 2013
Migration is widespread among birds, and the strength of the link between the breeding and wintering grounds, migratory connectivity, influences many ecological and evolutionary processes. Despite its importance, migratory connectivity is poorly estimated for most species. Traditionally, visual observations and bird ringing have been used to monitor migration, but these methods require more effort for relatively little return. Genetic markers and stable isotope signatures have increasingly been used to study connectivity. Each approach has its distinct strengths and weaknesses, and as is often the case, a combination may yield the most insight. In this issue of Molecular Ecology, Rundel and colleagues (2013) present a novel Bayesian statistical framework in which genetics and stable isotope data can be combined to improve the assignment of individuals to different winter or breeding regions. The development of such new statistical methods combined with the increasing number and ease of access of isotopic and genetic data sets will greatly enhance our understanding of migratory connectivity. Add to this the developments of miniature devices to track movements of individuals, and the field is destined to make major progression in the decades to come. © 2013 John Wiley & Sons Ltd.
Bostock M.G.,University of British Columbia
Tectonophysics | Year: 2013
The Moho in subduction zones exists in two distinct forms, one associated with the subducting oceanic plate and second with the overriding plate. The seismic expression of both forms is linked to the nature of a landward dipping, low-velocity zone (LVZ) that has been detected in a majority of subduction zones about the globe and that approximately coincides with Wadati-Benioff seismicity. We review seismic studies that constrain the properties of the LVZ in Cascadia where it has been extensively studied for over a quarter century. A model in which the LVZ is identified with hydrated pillow basalts and sheeted dikes of oceanic crustal Layer 2, is consistent with available geological and geophysical data, and reconciles previously conflicting interpretations. In this model, the upper oceanic crust is hydrated through intense circulation at the ridge and becomes overpressured upon subduction as a result of metamorphic dehydration reactions combined with an impermeable plate boundary above and a low porosity gabbroic Layer 3 below. The resulting seismic velocity contrast (approaching 50% for S-waves) significantly overwhelms that of a weaker, underlying oceanic Moho. At greater depths, oceanic crust undergoes eclogitization in a top-down sense leading to gradual disappearance of the LVZ. The large volume change accompanying eclogitization is postulated to rupture the plate boundary allowing fluids to penetrate the cooled, forearc mantle wedge. Pervasive serpentinization and free fluids reduce velocities within the wedge, thereby diminishing, erasing or even inverting the seismic contrast associated with the Moho of the overriding plate. This model is tested against observations of LVZs and forearc mantle structure worldwide. © 2012 Elsevier B.V.
Koga Y.,University of British Columbia
Physical Chemistry Chemical Physics | Year: 2013
The wording "hydrophobicity/hydrophilicity" has been used in a loose manner based on human experiences. We have devised a more quantitative way to redefine "hydrophobes" and "hydrophiles" in terms of the mole fraction dependence pattern of one of the third derivative quantities, the enthalpic interaction between solute molecules. We then devised a thermodynamic methodology to characterize the effect of a solute on H2O in terms of its hydrophobicity and/or hydrophilicity. We use a thermodynamic signature, the enthalpic interaction of 1-propanol, HE1P1P, to monitor how the test solute modifies H2O. By this method, characterization is facilitated by two indices; one pertaining to its hydrophobicity and the other its hydrophilicity. Hence differences among amphiphiles are quantified in a two-dimensional manner. Furthermore, an individual ion can be characterized independent of a counter ion. By using this methodology, we have studied the effects on H2O of a number of solutes, and gained some important new insights. For example, such commonly used examples of hydrophobes in the literature as tetramethyl urea, trimethylamine-N-oxide, and tetramethylammonium salts are in fact surprisingly hydrophilic. Hence the conclusions about "hydrophobes" using these samples ought to be interpreted with caution. The effects of anions on H 2O found by this methodology are in the same sequence of the Hofmeister ranking, which will no doubt aid a further investigation into this enigma in biochemistry. Thus, it is likely that this methodology could play an important role in the characterization of the effects of solutes in H 2O, and a perspective view may be useful. Here, we describe the basis on which the methodology is developed and the methodology itself in m.ore detail than given in individual papers. We then summarize the results in two dimensional hydrophobicity/hydrophilicity maps. This journal is © the Owner Societies 2013.
Keeling P.J.,University of British Columbia
Annual Review of Plant Biology | Year: 2013
Plastids (chloroplasts) have long been recognized to have originated by endosymbiosis of a cyanobacterium, but their subsequent evolutionary history has proved complex because they have also moved between eukaryotes during additional rounds of secondary and tertiary endosymbioses. Much of this history has been revealed by genomic analyses, but some debates remain unresolved, in particular those relating to secondary red plastids of the chromalveolates, especially cryptomonads. Here, I examine several fundamental questions and assumptions about endosymbiosis and plastid evolution, including the number of endosymbiotic events needed to explain plastid diversity, whether the genetic contribution of the endosymbionts to the host genome goes far beyond plastid-targeted genes, and whether organelle origins are best viewed as a singular transition involving one symbiont or as a gradual transition involving a long line of transient food/symbionts. I also discuss a possible link between transporters and the evolution of protein targeting in organelle integration. © Copyright ©2013 by Annual Reviews. All rights reserved.
Mitchell S.J.,University of British Columbia
Forestry | Year: 2013
Windthrow is all too often looked at as an exceptional, catastrophic phenomenon rather than a recurrent natural disturbance that falls within the spectrum of chronic and acute effects of wind on forests, and that drives ecosystem patterns and processes. This paper provides an integrative overview of the nature, contributing factors and impacts of wind-caused disturbance in forests, including its effects on trees, stands, landscapes and soils. Windthrow is examined through the integrating concepts of: the capacity of trees for acclimative growth, the limitation of acclimative growth under inter-tree competition, the recurrent nature of severe weather, how terrain and soil conditions affect local stand vulnerability and the effect of recurrent windthrow on stand dynamics and soils. Windthrow management should take place within a framework of general risk management, with evaluation of the likelihood, severity and potential impacts of wind damage considered - with reference to the broad and specific aims of management. There is much to be gained from interdisciplinary communication about the nature and consequences of recurrent wind damage. There are opportunities for climatologists, engineers, ecologists, geomorphologists and others to develop integrative process models at the tree, stand and landscape scales that will improve our collective understanding, and inform management decision-making. © Institute of Chartered Foresters, 2012. All rights reserved.
Chagnon P.-L.,Universite de Sherbrooke |
Bradley R.L.,Universite de Sherbrooke |
Maherali H.,University of Guelph |
Klironomos J.N.,University of British Columbia
Trends in Plant Science | Year: 2013
Despite the growing appreciation for the functional diversity of arbuscular mycorrhizal (AM) fungi, our understanding of the causes and consequences of this diversity is still poor. In this opinion article, we review published data on AM fungal functional traits and attempt to identify major axes of life history variation. We propose that a life history classification system based on the grouping of functional traits, such as Grime's C-S-R (competitor, stress tolerator, ruderal) framework, can help to explain life history diversification in AM fungi, successional dynamics, and the spatial structure of AM fungal assemblages. Using a common life history classification framework for both plants and AM fungi could also help in predicting probable species associations in natural communities and increase our fundamental understanding of the interaction between land plants and AM fungi. © 2013 Elsevier Ltd.
Van Petegem F.,University of British Columbia
Journal of Molecular Biology | Year: 2015
The endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) form major intracellular Ca2 + stores. Ryanodine receptors (RyRs) are large tetrameric ion channels in the SR and ER membranes that can release Ca2 + upon triggering. With molecular masses exceeding 2.2 MDa, they represent the pinnacle of ion channel complexity. RyRs have adopted long-range allosteric mechanisms, with pore opening resulting in conformational changes over 200 Å away. Together with tens of protein and small molecule modulators, RyRs have adopted rich and complex regulatory mechanisms. Structurally related to inositol-1,4,5-trisphosphate receptors (IP3Rs), RyRs have been studied extensively using cryo-electron microscopy (cryo-EM). Along with more recent X-ray crystallographic analyses of individual domains, these have resulted in pseudo-atomic models. Over 500 mutations in RyRs have been linked to severe genetic disorders, which underscore their role in the contraction of cardiac and skeletal muscles. Most of these have been linked to gain-of-function phenotypes, resulting in premature or prolonged leak of Ca2 + in the cytosol. This review outlines our current knowledge on the structure of RyRs at high and low resolutions, their relationship to IP3Rs, an overview of the most commonly studied regulatory mechanisms, and models that relate disease-causing mutations to altered channel function. © 2014 Elsevier Ltd. All rights reserved.
van Pel D.M.,University of British Columbia
G3 (Bethesda, Md.) | Year: 2013
The concept of synthetic lethality has gained popularity as a rational guide for predicting chemotherapeutic targets based on negative genetic interactions between tumor-specific somatic mutations and a second-site target gene. One hallmark of most cancers that can be exploited by chemotherapies is chromosome instability (CIN). Because chromosome replication, maintenance, and segregation represent conserved and cell-essential processes, they can be modeled effectively in simpler eukaryotes such as Saccharomyces cerevisiae. Here we analyze and extend genetic networks of CIN cancer gene orthologs in yeast, focusing on essential genes. This identifies hub genes and processes that are candidate targets for synthetic lethal killing of cancer cells with defined somatic mutations. One hub process in these networks is DNA replication. A nonessential, fork-associated scaffold, CTF4, is among the most highly connected genes. As Ctf4 lacks enzymatic activity, potentially limiting its development as a therapeutic target, we exploited its function as a physical interaction hub to rationally predict synthetic lethal interactions between essential Ctf4-binding proteins and CIN cancer gene orthologs. We then validated a subset of predicted genetic interactions in a human colorectal cancer cell line, showing that siRNA-mediated knockdown of MRE11A sensitizes cells to depletion of various replication fork-associated proteins. Overall, this work describes methods to identify, predict, and validate in cancer cells candidate therapeutic targets for tumors with known somatic mutations in CIN genes using data from yeast. We affirm not only replication stress but also the targeting of DNA replication fork proteins themselves as potential targets for anticancer therapeutic development.
Freeman H.J.,University of British Columbia
World Journal of Gastroenterology | Year: 2012
In the past, there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity. Now, a variety of new biological monoclonal antibody agents, usually administered by infusion, have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents, adverse effects have been documented, including apparently new forms of immune-mediated inflammatory bowel disease. In some, only limited symptoms have been recorded, but in others, severe colitis with serious complications, such as bowel perforation has been recorded. In others, adverse effects may have a direct vascular or ischemic basis, while other intestinal effects may be related to a superimposed infection. Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases, or be responsible for disease exacerbation. Dramatic and well documented side effects have been observed with ipilimumab, a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4, a key negative feedback regulator of the T-cell anti-tumor response. This agent has frequently been used in the treatment of different malignancies, notably, malignant melanoma. Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated. One of these is a form of enterocolitis that may be severe, and occasionally, fatal. Other agents include rituximab (an anti-CD20 monoclonal antibody), bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents, including infliximab, adalimumab and etanercept. © 2012 Baishideng. All rights reserved.
Muja M.,BitLit Media Inc |
Lowe D.G.,University of British Columbia
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2014
For many computer vision and machine learning problems, large training sets are key for good performance. However, the most computationally expensive part of many computer vision and machine learning algorithms consists of finding nearest neighbor matches to high dimensional vectors that represent the training data. We propose new algorithms for approximate nearest neighbor matching and evaluate and compare them with previous algorithms. For matching high dimensional features, we find two algorithms to be the most efficient: the randomized k-d forest and a new algorithm proposed in this paper, the priority search k-means tree. We also propose a new algorithm for matching binary features by searching multiple hierarchical clustering trees and show it outperforms methods typically used in the literature. We show that the optimal nearest neighbor algorithm and its parameters depend on the data set characteristics and describe an automated configuration procedure for finding the best algorithm to search a particular data set. In order to scale to very large data sets that would otherwise not fit in the memory of a single machine, we propose a distributed nearest neighbor matching framework that can be used with any of the algorithms described in the paper. All this research has been released as an open source library called fast library for approximate nearest neighbors (FLANN), which has been incorporated into OpenCV and is now one of the most popular libraries for nearest neighbor matching. © 2014 IEEE.
Davies J.,University of British Columbia
Current Opinion in Chemical Biology | Year: 2011
There is a dire need for new antibiotics; commercial discovery programs have essentially dried up and there is talk of 'a return to the pre-antibiotic era'. Natural products are an inexhaustible source of bioactive compounds (antibiotics among them), and recent technical advances such as DNA sequencing and bioinformatics offer new approaches to small molecule discovery. Given that nucleotide sequence studies of actinomycetes genomes reveal the presence of 20 or more pathways for the synthesis of bioactive compounds, 'mining' these sequences offers the potential of expanding the repertoire of antibiotics and other drugs. Combined with advanced chemical separation and characterization techniques, the construction of large chemically diverse libraries of bioactive compounds for therapeutic applications is a realistic near-term goal. © 2010 Elsevier Ltd.
Jilkine A.,University of Texas Southwestern Medical Center |
Edelstein-Keshet L.,University of British Columbia
PLoS Computational Biology | Year: 2011
Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant) in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons), and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness. © 2011 Jilkine, Edelstein-Keshet.
Froese T.M.,University of British Columbia
Automation in Construction | Year: 2010
Changes brought about from advances in information and communication technology for the architecture, engineering, and construction industries (construction ICT) are not purely technical, but must be accompanied by changes to the management processes. Elsewhere, we have discussed a framework for project information management in construction. This paper addresses changes to the practice of project management as a whole. Broadly, it suggests a unified approach to project management that involves defining a set of widely-applicable common views of the project information, explicitly defining the inter-relationships between the information in these different views, and modifying project management tools and procedures to work with these integrated views. © 2009 Elsevier B.V. All rights reserved.
Pai D.K.,University of British Columbia
Journal of Biomechanics | Year: 2010
Most current models of musculoskeletal dynamics lump a muscle's mass with its body segment, and then simulate the dynamics of these body segments connected by joints. As shown here, this popular approach leads to errors in the system's inertia matrix and hence in all aspects of the dynamics. Two simplified mathematical models were created to capture the relevant features of monoarticular and biarticular muscles, and the errors were analyzed. The models were also applied to two physiological examples: the triceps surae muscles that plantar flex the human ankle and the biceps femoris posterior muscle of the rat hind limb. The analysis of errors due to lumping showed that these errors can be large. Although the errors can be reduced in some postures, they cannot be easily eliminated in models that use segment lumping. Some options for addressing these errors are discussed. © 2010 Elsevier Ltd.
Schajer G.S.,University of British Columbia
Experimental Mechanics | Year: 2010
Relaxation methods, also called "destructive" methods, are commonly used to evaluate residual stresses in a wide range of engineering components. While seemingly less attractive than non-destructive methods because of the specimen damage they cause, the relaxation methods are very frequently the preferred choice because of their versatility and reliability. Many different methods and variations of methods have been developed to suit various specimen geometries and measurement objectives. Previously, only specimens with simple geometries could be handled, but now the availability of sophisticated computational tools and of high-precision machining and measurement processes has greatly expanded the scope of the relaxation methods for residual stress evaluation. This paper reviews several prominent relaxation methods, describes recent advances, and indicates some promising directions for future developments. © 2010 Society for Experimental Mechanics.
Gopaluni R.B.,University of British Columbia
Journal of Process Control | Year: 2010
This article presents an algorithm for identification of nonlinear state-space models when the "true" model structure of a process is unknown. In order to estimate the parameters in a state-space model, one needs to know the model structure and have an estimate of states. An approximation of the model structure is obtained using radial basis functions centered around a maximum a posteriori estimate of the state trajectory. A particle filter approximation of smoothed states is then used in conjunction with expectation maximization algorithm for estimating the parameters. The proposed approach is extended to handle missing observations and illustrated through a real application. © 2010 Elsevier Ltd. All rights reserved.
Schoof C.,University of British Columbia
Journal of Fluid Mechanics | Year: 2012
Ice-stream shear margins are the lateral boundaries of narrow, fast-flowing bands of ice within an ice sheet. We develop a theory for the migration of shear margins over time driven by viscous dissipation of heat within the ice, focusing on widening of the ice stream. The location of the margin is modelled as a transition from a cold to a temperate ice-sheet bed, and simultaneously as the transition from no slip to free slip at the same location. The temperature field in the ice is affected by intense shear heating as well as by the migration velocity of the margin (i.e. by the widening rate of the ice stream); if migration is too fast, there is little time for the ice to warm up and the margin remains cold, causing the bed to freeze. This suppresses widening. Conversely, if the migration speed is too slow, the ice in the margin warms up, causing the bed on the far side of the cold-temperate transition to reach the melting point, and migration to speed up. Using a Wiener-Hopf method, we show that for a given far-field shear stress, geothermal heat flux, and ice geometry, there is a single migration velocity that balances the two effects and permits widening at a steady rate. This velocity increases with the far-field lateral shear stress imposed by the ice stream, which controls shear heating in the margin. Our results also indicate that (i) a region of temperate ice must form in the margin, and that (ii) lateral advection of ice may play a significant role in controlling migration speeds. © 2012 Cambridge University Press.
Tupper K.W.,University of British Columbia
Critical Public Health | Year: 2014
In the late nineteenth and early twentieth century in North America, public health and social reform advocates were quick to identify and exploit the nascent modern institution of public schools as opportune spaces in which to advance their progressive projects. In particular, psychoactive substance use (at first primarily alcohol drinking) and sexuality were regarded as two domains of morally-charged social activity in which desired attitudinal and behavioural outcomes could be achieved through school-based education. Since the advent of these early public health or 'social hygiene' efforts in schools, political responses and modern Western cultural norms about both drugs and sexuality have undergone significant transformation over the course of the twentieth century. At the same time, research on purported health or social risks of substance use and sexual activity - and their prevention and mitigation among young people - has burgeoned as a field of professional practice and academic inquiry. This article undertakes a brief comparative review of historical and contemporary approaches to school-based sexuality and drug education in North America. In so doing, it also explores how scientific knowledge about the topics of sex and drugs, and the corollary project of school-based 'prevention' in these domains, has been shaped by evolving ideological and cultural forces. It concludes that the issues of sexuality and drug use - still steeped in conceptions of moral purity and pollution - are likely to remain strongly contested terrain for school-based education. © 2013 Taylor & Francis.
Kleiger G.,University of Nevada, Las Vegas |
Mayor T.,University of British Columbia
Trends in Cell Biology | Year: 2014
Eukaryotic cells are equipped to degrade proteins via the ubiquitin-proteasome system (UPS). Proteins become degraded upon their conjugation to chains of ubiquitin where they are then directed to the 26S proteasome, a macromolecular protease. The transfer of ubiquitin to proteins and their subsequent degradation are highly complex processes, and new research is beginning to uncover the molecular details of how ubiquitination and degradation take place in the cell. We review some of the new data providing insights into how these processes occur. Although distinct mechanisms are often observed, some common themes are emerging for how the UPS guides protein substrates through their final journey. © 2013 Elsevier Ltd.
Cho Y.M.,Seoul National University |
Fujita Y.,Asahikawa University |
Kieffer T.J.,University of British Columbia
Annual Review of Physiology | Year: 2014
Glucagon-like peptide-1 (GLP-1), an incretin hormone secreted primarily from the intestinal L-cells in response to meals, modulates nutrient homeostasis via actions exerted in multiple tissues and cell types. GLP-1 and its analogs, as well as compounds that inhibit endogenous GLP-1 breakdown, have become an effective therapeutic strategy for many subjects with type 2 diabetes. Here we review the discovery of GLP-1; its synthesis, secretion, and elimination from the circulation; and its multiple pancreatic and extrapancreatic effects. Finally, we review current options for GLP-1-based diabetes therapy, including GLP-1 receptor agonism and inhibition of GLP-1 breakdown, as well as the benefits and drawbacks of different modes of therapy and the potential for new therapeutic avenues. © Copyright ©2014 by Annual Reviews. All rights reserved.
Chan K.K.,University of British Columbia
The Cochrane database of systematic reviews | Year: 2014
Thoracic aortic dissection (TAD) is a severe and often lethal complication in people with hypertension. Current practice in the treatment of chronic type B aortic dissections is the use of beta-blockers as first-line therapy to decrease aortic wall stress. Other antihypertensive medications, such as calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), have been suggested for the medical therapy of type B TAD. To assess the effects of first-line beta-blockers compared with other first-line antihypertensive drug classes for treating chronic type B TAD. We searched the Database of Abstracts of Reviews of Effects (DARE) for related reviews. We searched the Hypertension Group Specialised Register (1946 to 26 January 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1), MEDLINE (1946 to 24 January 2014), MEDLINE In-Process, EMBASE (1974 to 24 January 2014) and ClinicalTrials.gov (to 26 January 2014). We considered randomized controlled trials (RCTs) comparing different antihypertensive medications in the treatment of chronic type B TAD to be eligible for inclusion. Total mortality rate was the primary outcome of this review. Secondary outcomes included total non-fatal adverse events relating to TADs and number of people not requiring surgical treatment. Two review authors (KC, PL) independently reviewed titles and abstracts and decided on studies to include based on the inclusion criteria. We resolved discrepancies between the two review authors by discussion. After a thorough review of the search results, we identified no studies that met the inclusion criteria. We did not find any RCTs that compared first-line beta-blockers with other first-line antihypertensive medications for the treatment of chronic type B TAD. Therefore, there is no RCT evidence to support the current guidelines recommending the use of beta-blockers. RCTs are required to assess the benefits and harms of beta-blockers and other antihypertensive medications as first-line treatment of chronic type B TAD.
Kindrachuk J.,University of British Columbia
Mini reviews in medicinal chemistry | Year: 2010
Host defence peptides (HDPs) are multi-functional inducers and effectors of host immunity. Through their direct antimicrobial activity HDPs have for been successfully utilized for many years as topical antibiotics and food preservatives. The more recent appreciation of HDP immunomodulatory activities offers additional opportunities for application as systemic antimicrobials, anti-inflammatory agents and vaccine adjuvants. HDPs have demonstrated proof-of-principle success in each of these applications. Optimization of HDPs for these objectives will benefit from a greater comprehension of the structural basis of their various activities. Such an understanding will facilitate rational design and/or selection of peptides with enhanced properties. This is complicated, however, by the diversity of HDP sequences, structures and mechanisms of action. Furthermore, while the ability of HDPs to undergo template-driven formation of bioactive structures enables these small peptides to perform a diverse range of actions it also complicates efforts to understand contributions of particular structural features to specific activities. With recognition of these limitations, but consideration of the emerging importance of this exciting class of molecules, we review the current understanding of the structural basis of select HDP activities as well as present strategies for HDP selection and optimization.
Baron A.S.,University of British Columbia
Child Development Perspectives | Year: 2015
Implicit attitudes form in the 1st years of life and change little across development. By age 6, children's implicit intergroup attitudes are sensitive to the cultural standing of their group relative to other groups in their milieu, such that individuals prefer their own group less when the comparison group is of higher cultural standing. In this article, I consider the claim that the stability of the magnitude of implicit attitudes across development reflects the absence of meaningful developmental change. I also examine the extent to which the developmental stability for implicit intergroup attitudes describes similarly the ontogeny of other forms of implicit associations, including stereotypes, identity, and self-esteem. And I characterize the landscape of what may be changing across these formative years in children's implicit intergroup cognition. © 2015 The Society for Research in Child Development.
Eaves C.J.,Terry Fox Laboratory |
Eaves C.J.,University of British Columbia
Blood | Year: 2015
Hematopoietic stem cell (HSC) research took hold in the 1950s with the demonstration that intravenously injected bone marrow cells can rescue irradiated mice from lethality by reestablishing blood cell production. Attempts to quantify the cells responsible led to the discovery of serially transplantable, donor-derived, macroscopic, multilineage colonies detectable on the spleen surface 1 to 2 weeks posttransplant. The concept of self-renewing multipotent HSCs was born, but accompanied by perplexing evidence of great variability in the outcomes of HSC self-renewal divisions. The next 60 years saw an explosion in the development and use of more refined tools for assessing the behavior of prospectively purified subsets of hematopoietic cells with blood cell-producing capacity. These developments have led to the formulation of increasingly complex hierarchical models of hematopoiesis and a growing list of intrinsic and extrinsic elements that regulate HSC cycling status, viability, self-renewal, and lineage outputs. More recent examination of these properties in individual, highly purified HSCs and analyses of their perpetuation in clonally generated progeny HSCs have now provided definitive evidence of linearly transmitted heterogeneity in HSC states. These results anticipate the need and use of emerging new technologies to establish models that will accommodate such pluralistic features of HSCs and their control mechanisms. © 2015 by The American Society of Hematology.
Dufour A.,University of British Columbia
Frontiers in Bioscience - Scholar | Year: 2015
Organisms have evolved to react to stress, tissue damage and pathogen invasion to assure their survival. Leukocytes are the primary responders and they regulate repair, immune defense and inflammation with the aid of a wide variety of other cells (e.g. epithelial, fibroblasts). To assure proper responses, a plethora of proteins are involved including signaling molecules, chemokines and proteases to orchestrate a step-by-step reaction. Inflammation is an essential biological process, however, when it persists, it can lead to various diseases that are challenging to heal or cure. The technologies and techniques covered in this book chapter can be applied to study all proteases and their inhibitors although will be centered on the matrix metalloproteinases (MMPs). It will focus on the proteolysis performed by MMPs, their various beneficial and detrimental effects in inflammation and the novel methods to study their roles on human diseases. © 1996-2015.
Rozali M.,University of British Columbia
Physical Review Letters | Year: 2012
We study the interface between a fractional topological insulator and an ordinary insulator, both described using holography. By turning on a chemical potential we induce a finite density of matter localized at the interface. These are gapless surface excitations which are expected to have a fermionic character. We study the thermodynamics of the system, finding a symmetry preserving compressible state at low temperatures, whose excitations exhibit hyperscaling violation. These results are consistent with the expectation of gapless fermionic excitations forming a Fermi surface at finite density. © 2012 American Physical Society.
Lamers Y.,University of British Columbia
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2011
Purpose of Review: Nutritional status assessment is a critical tool for the identification of nutrient deficiencies or excesses in individual healthcare and epidemiologic screening. Because low but 'normal' status of folate, vitamin B-12, and vitamin B-6 have been associated with an increased risk of chronic diseases, research has focused on defining sensitive indicators of B-vitamin status and on the development and validation of analytical methods for their quantification. Recent Findings: With the increasing availability and more user-friendly configuration of liquid chromatograph-tandem mass spectrometers (LC-MS/MS), numerous analytical methods for determination of B-vitamin indicators by LC-MS/MS have been developed over the last years. These methods include folate assays for simultaneous determination of numerous folate forms at their specific reduction level. The functional indicators for vitamin B-12 status are plasma methylmalonic acid and total homocysteine and can be measured, either individually or in combination, by high-throughput analysis using LC-MS/MS. Methods for vitamin B-6 status assessment are multianalyte platforms that determine vitamin B-6 forms and functional indicators by the same assay. Summary: The high sensitivity, selectivity, and specificity of isotope-dilution LC-MS/MS [and gas chromatography-mass spectrometry (GC-MS)] techniques have allowed the development of reference methods and the creation of multianalyte platforms. The additional convenience of automated sample preparation enables high sample throughput and makes those sensitive methods prospective analytical candidates for larger settings including clinical laboratories. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Bell K.,University of British Columbia |
Keane H.,Australian National University
Social Science and Medicine | Year: 2014
The idea that drug use in 'softer' forms leads to 'harder' drug use lies at the heart of the gateway theory, one of the most influential models of drug use of the twentieth century. Although hotly contested, the notion of the 'gateway drug' continues to rear its head in discussions of drug use-most recently in the context of electronic cigarettes. Based on a critical reading of a range of texts, including scholarly literature and media reports, we explore the history and gestation of the gateway theory, highlighting the ways in which intersections between academic, media and popular accounts actively produced the concept. Arguing that the theory has been critical in maintaining the distinction between 'soft' and 'hard' drugs, we turn to its distinctive iteration in the context of debates about e-cigarettes. We show that the notion of the 'gateway' has been transformed from a descriptive to a predictive model, one in which nicotine is constituted as simultaneously 'soft' and 'hard'-as both relatively innocuous and incontrovertibly harmful. © 2014 Elsevier Ltd.
Freeman H.J.,University of British Columbia
World Journal of Gastroenterology | Year: 2014
Crohn's disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract. Occasionally, so-called metastatic disease occurs in extra-intestinal sites. Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues. Genetic, epigenetic and environmental factors appear to play a role. Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance. The disorder occurs over a broad age spectrum, from early childhood to late adulthood. More than 80% are diagnosed before age 40 years usually with terminal ileal and colonic involvement. Pediatric-onset disease is more severe and more extensive, usually with a higher chance of upper gastrointestinal tract disease, compared to adult-onset disease. Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications (i.e., fistula, abscess). Although prolonged remission may occur, discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process. Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis. Until now, treatment has focused on removing risk factors, particularly cigarette smoking, and improving symptoms. In clinical trials, clinical remission is largely defined as improved numerical and endoscopic indices for "mucosal healing". "Deep remission" is a conceptual, more "extended" goal that may or may not alter the long-term natural history of the disease in selected patients, albeit at a significant risk for treatment complications, including serious and unusual opportunistic infections. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
Quamme G.A.,University of British Columbia
American Journal of Physiology - Cell Physiology | Year: 2010
A large number of mammalian Mg2+ transporters have been hypothesized on the basis of physiological data, but few have been investigated at the molecular level. The recent identification of a number of novel proteins that mediate Mg2+ transport has enhanced our understanding of how Mg2+ is translocated across mammalian membranes. Some of these transporters have some similarity to those found in prokaryocytes and yeast cells. Human Mrs2, a mitochondrial Mg2+ channel, shares many of the properties of the bacterial CorA and yeast Alr1 proteins. The SLC41 family of mammalian Mg2+ transporters has a similarity with some regions of the bacterial MgtE transporters. The mammalian ancient conserved domain protein (ACDP) Mg2+ transporters are found in prokaryotes, suggesting an ancient origin. However, other newly identified mammalian transporters, including TRPM6/7, MagT, NIPA, MMgT, and HIP14 families, are not represented in prokaryotic genomes, suggesting more recent development. MagT, NIPA, MMgT, and HIP14 transporters were identified by differential gene expression using microarray analysis. These proteins, which are found in many different tissues and subcellular organelles, demonstrate a diversity of structural properties and biophysical functions. The mammalian Mg2+ transporters have no obvious amino acid similarities, indicating that there are many ways to transport Mg2+ across membranes. Most of these proteins transport a number of divalent cations across membranes. Only MagT1 and NIPA2 are selective for Mg2+. Many of the identified mammalian Mg2+ transporters are associated with a number of congenital disorders encompassing a wide range of tissues, including intestine, kidney, brain, nervous system, and skin. It is anticipated that future research will identify other novel Mg 2+ transporters and reveal other diseases. Copyright © 2010 the American Physiological Society.
Shen S.,University of Alberta |
Li X.-F.,University of Alberta |
Cullen W.R.,University of British Columbia |
Weinfeld M.,University of Alberta |
Le X.C.,University of Alberta
Chemical Reviews | Year: 2013
Chronic exposure to arsenic from groundwater has been recognized to cause the largest environmental health disaster in the world, putting more than 100 million people at risk of cancer and other arsenic-related diseases. Depletion of ATP by arsenate has been observed in cellular systems. However, the replacement of phosphate in DNA by arsenic is not firmly established. The toxicity of trivalent arsenicals likely occurs through the interaction of trivalent arsenic species with sulfhydryl groups in proteins. Arsenic binding to a specific protein could alter the conformation and function of the protein as well as its recruitment of and interaction with other functional proteins. Therefore, there has been much emphasis on studies of arsenic binding to proteins, for the purpose of understanding arsenic toxicity and developing arsenic-based therapeutics.
Conibear E.,University of British Columbia
Current Opinion in Cell Biology | Year: 2010
Receptor-mediated endocytosis is important for the selective internalization of membrane proteins. In mammals, clathrin, adaptors, and dynamin play prominent roles in regulating cargo selection and vesicle formation. Endocytosis in yeast is generally conserved, but exhibits significant and perplexing differences in the relative importance of clathrin adaptors, dynamin-like proteins, and actin. Recent studies are now reconciling divergent views of endocytic processes in yeast and mammals. The discovery of cargo-specific functions for yeast homologs of mammalian clathrin adaptors has rapidly expanded the number of endocytic adaptors in yeast. Moreover, unifying models have been advanced to explain how dynamin, actin, and membrane-deforming proteins drive membrane scission. While differences remain, discoveries from each system will continue to inform the other. © 2010 Elsevier Ltd.
Gabora L.,University of British Columbia
Physics of Life Reviews | Year: 2013
Dawkins' replicator-based conception of evolution has led to widespread mis-application of selectionism across the social sciences because it does not address the paradox that necessitated the theory of natural selection in the first place: how do organisms accumulate change when traits acquired over their lifetime are obliterated? This is addressed by von Neumann's concept of a self-replicating automaton (SRA). A SRA consists of a self-assembly code that is used in two distinct ways: (1) actively deciphered during development to construct a self-similar replicant, and (2) passively copied to the replicant to ensure that it can reproduce. Information that is acquired over a lifetime is not transmitted to offspring, whereas information that is inherited during copying is transmitted. In cultural evolution there is no mechanism for discarding acquired change. Acquired change can accumulate orders of magnitude faster than, and quickly overwhelm, inherited change due to differential replication of variants in response to selection. This prohibits a selectionist but not an evolutionary framework for culture and the creative processes that fuel it. The importance non-Darwinian processes in biological evolution is increasingly recognized. Recent work on the origin of life suggests that early life evolved through a non-Darwinian process referred to as communal exchange that does not involve a self-assembly code, and that natural selection emerged from this more haphazard, ancestral evolutionary process. It is proposed that communal exchange provides an evolutionary framework for culture that enables specification of cognitive features necessary for a (real or artificial) societies to evolve culture. This is supported by a computational model of cultural evolution and a conceptual network based program for documenting material cultural history, and it is consistent with high levels of human cooperation. © 2013 Elsevier B.V.
Barr S.I.,University of British Columbia
Applied Physiology, Nutrition and Metabolism | Year: 2010
Sodium is a required nutrient; Adequate Intakes for adults range from 1200 to 1500 mg-day-1, depending on age. The Tolerable Upper Intake Level (UL) for sodium is 2300 mg-day-1 for adults, based on the relationship between sodium intake and increased blood pressure. Elevated blood pressure, which is prevalent among Canadians, is, in turn, a major risk factor for stroke, cardiovascular disease, and renal disease. Sodium intake is not the only determinant of blood pressure; other modifiable risk factors include relative mass, physical activity, overall dietary quality, and alcohol consumption. However, because >90% of adult Canadian men and two thirds of Canadian women have sodium intakes above the UL, Health Canada's Working Group on Dietary Sodium Reduction has been charged with developing, implementing, and overseeing a strategy to reduce Canadians' sodium intakes. It is estimated that ~75% of dietary sodium is added during food processing; in addition to taste and palatability, sodium also has functional roles in food manufacturing and preservation, although the amounts used often exceed those required. Because of the central role of processed foods in sodium intake, the strategy proposed by Health Canada's Working Group includes voluntary reduction of sodium in processed foods and foods sold in food service establishments. It will also include an education and awareness campaign, and research and surveillance. Initiatives to reduce sodium in other parts of the world have demonstrated that it will be challenging to reduce sodium intake to the recommended range and will likely require many years to accomplish.
Roemer T.,Merck |
Davies J.,University of British Columbia |
Giaever G.,University of Toronto |
Nislow C.,University of Toronto
Nature Chemical Biology | Year: 2012
The serendipitous discovery of penicillin inspired intensive research into how small molecules affect basic cellular processes and their potential to treat disease. Biochemical and genetic approaches have been fundamental for clarifying small-molecule modes of action. Genomic technologies have permitted the use of chemical-genetic strategies that comprehensively study compound-target relationships in the context of a living cell, providing a systems biology view of both the cellular targets and the interdependent networks that respond to chemical stress. These studies highlight the fact that in vitro determinations of mechanism rarely translate into a complete understanding of drug behavior in the cell. Here, we review key discoveries that gave rise to the field of chemical genetics, with particular attention to chemical-genetic strategies developed for bakers' yeast, their extension to clinically relevant microbial pathogens, and the potential of these approaches to affect antimicrobial drug discovery. © 2011 Nature America, Inc. All rights reserved.
Milsom W.K.,University of British Columbia
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2010
In 1941, August Krogh published a monograph entitled The Comparative Physiology of Respiratory Mechanisms (Philadelphia, PA: University of Pennsylvania Press, 1941). Since that time comparative studies have continued to contribute significantly to our understanding of the fundamentals of respiratory physiology and the adaptive trends in these processes that support a broad range of metabolic performance under demanding environmental conditions. This review specifically focuses on recent advances in our understanding of adaptive trends in respiratory control. Respiratory rhythm generators most likely arose from, and must remain integrated with, rhythm generators for chewing, suckling, and swallowing. Within the central nervous system there are multiple "segmental" rhythm generators, and through evolution there is a caudal shift in the predominant respiratory rhythm-generating site. All sites, however, may still be capable of producing or modulating respiratory rhythm under appropriate conditions. Expression of the respiratory rhythm is conditional on (tonic) input. Once the rhythm is expressed, it is often episodic as the basic medullary rhythm is turned on/off subject to a hierarchy of controls. Breathing patterns reflect differences in pulmonary mechanics resulting from differences in body wall and lung architecture and are modulated in different species by various combinations of upper and lower airway mechanoreceptors and arterial chemoreceptors to protect airways, reduce dead space ventilation, enhance gas exchange efficiency, and reduce the cost of breathing. Copyright © 2010 the American Physiological Society.
Stoessl A.J.,University of British Columbia
Movement Disorders | Year: 2015
Functional imaging may be particularly helpful for the assessment of levodopa (l-dopa) response and long-term complications of therapy in Parkinson's disease. Radiotracer imaging allows the quantitative determination of regional changes in blood flow and glucose metabolism, as well as alterations in brain connectivity and network activation and changes in dopamine receptors, non-dopaminergic neurotransmitter systems, and to a lesser extent, signaling pathways downstream to dopamine receptors. The focus of the present article, however, is the application of positron emission tomography (PET) to study the central pharmacokinetics of l-dopa. Radioligands with limited affinity for the dopamine D2 receptor are sensitive to changes in the levels of synaptic dopamine and can accordingly provide helpful insights into the magnitude and time course of dopamine release after l-dopa. Prolonged fluorodopa PET scans can be used to estimate the rate of dopamine turnover. Studies performed with these techniques have demonstrated increased dopamine turnover and increased but shorter duration release of dopamine after l-dopa as Parkinson's disease (PD) progresses, increased release of dopamine in patients with l-dopa-induced dyskinesia, and that aberrant patterns of dopamine release may actually predict the future development of motor fluctuations. Taken together, the studies provide in vivo validation for the hypothesis that pulsatile stimulation of dopamine receptors plays a critical role in the emergence of long-term motor complications of therapy. Similar approaches can be used to study the non-motor complications of PD and its treatment. © 2014 International Parkinson and Movement Disorder Society.
Brandizzi F.,Michigan State University |
Wasteneys G.O.,University of British Columbia
Plant Journal | Year: 2013
Movement of secretory organelles is a fascinating yet largely mysterious feature of eukaryotic cells. Microtubule-based endomembrane and organelle motility utilizing the motor proteins dynein and kinesin is commonplace in animal cells. In contrast, it has been long accepted that intracellular motility in plant cells is predominantly driven by myosin motors dragging organelles and endomembrane-bounded cargo along actin filament bundles. Consistent with this, defects in the acto-myosin cytoskeleton compromise plant growth and development. Recent findings, however, challenge the actin-centric view of the motility of critical secretory organelles and distribution of associated protein machinery. In this review, we provide an overview of the current knowledge on actin-mediated organelle movement within the secretory pathway of plant cells, and report on recent and exciting findings that support a critical role of microtubules in plant cell development, in fine-tuning the positioning of Golgi stacks, as well as their involvement in cellulose synthesis and auxin polar transport. These emerging aspects of the biology of microtubules highlight adaptations of an ancestral machinery that plants have specifically evolved to support the functioning of the acto-myosin cytoskeleton, and mark new trends in our global appreciation of the complexity of organelle movement within the plant secretory pathway. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.
Whalley Hammell K.R.,University of British Columbia
Scandinavian Journal of Occupational Therapy | Year: 2013
Aims: The occupational therapy profession has long proclaimed its commitment to a client-centred philosophy of practice and the assumption that occupational therapists consistently practice in a client-centred manner has become central to the profession's self-image and public rhetoric. However, client-centred practice has been subjected to little critical reflection within the occupational therapy profession. The aim of this paper is to foster critical reflection concerning the authenticity and veracity of the profession's commitment to client-centred practices. Major findings: Client-centred practice is defined without evident reference to clients' perspectives. Few occupational therapy researchers have sought clients' perceptions of the client-centred nature of their occupational therapy services. Occupational therapy research is neither consistently undertaken in a collaborative manner, nor are the profession's theories developed through explicit reference to a diversity of clients' perspectives. Professional practices and service evaluations do not consistently seek clients' viewpoints. Client-centred rhetoric is politically expedient and may be a professionalizing strategy employed to increase status and entrench power. Practice conclusion: Although exemplary client-centred occupational therapy practices exist, evidence suggests that the profession does not adhere consistently to its espoused client-centred principle in all its practices. The client-centred practice of occupational therapy should be subjected to assiduous critical reflection. © 2013 Informa Healthcare.
Livesley J.,University of British Columbia
Psychopathology | Year: 2013
Background: The compilation of DSM-5 presented a substantial opportunity to develop a coherent, evidence-based classification of personality disorder. The irremediable problems with DSM-IV are widely recognized, the field seemed ready for change, and the data and methods for constructing a scientific classification are readily available. Rather than seize this opportunity, DSM-5 advanced an incoherent proposal lacking in evidential support and too poorly organized for clinical use. Methods: This article examines the problems with the proposal based on a consideration of the basic requirements of a satisfactory classification. It is suggested that an adequate system should have an explicit and coherent conceptual structure, be based on the best available scientific evidence, possess clinical utility, and be as parsimonious as possible. Results: The DSM-5 proposal fails to meet these criteria. Problems with the product and process suggest the need for a radical reconsideration of how personality disorders are classified and how classifications are compiled. Conclusions: The article proposes that greater emphasis be placed on developing a classification that provides the diagnostic information clinicians need to treat personality disorder and that future classifications should be constructed through an explicit process that is open to public scrutiny. Copyright © 2013 S. Karger AG, Basel.
Montaner J.S.G.,University of British Columbia
Topics in Antiviral Medicine | Year: 2013
In British Columbia, Canada, intensive efforts have been made to implement and maintain a treatment-as-prevention strategy among the HIV-infected population. Acceleration of antiretroviral therapy coverage has resulted in a substantial increase in the median CD4+ cell count at which treatment is initiated and a dramatic decline in community plasma HIV RNA levels. This has resulted in a reduction in diagnoses of new cases of HIV infection, including among injection drug users. Proportions of individuals with viral suppression have steadily increased and the expansion of antiretroviral therapy coverage has not been associated with increased levels of HIV resistance. Further, adoption of routine HIV testing in acute care settings has been very well accepted and has captured new cases at a rate of 5 per 1000 tests outside of high-risk populations, offering an additional strategy for identifying and linking at least some individuals with undiagnosed HIV infection to care. Deriving optimal individual and social health outcomes in HIV infection requires improvement in every element of the cascade of care. © 2013, IAS-USA.
Mayor T.,University of British Columbia
Nature Cell Biology | Year: 2012
The endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway, which orchestrates the degradation of ER proteins by the proteasome, involves a plethora of proteins with diverse functions. Using a combination of proteomic and genetic approaches, a recent study provides fresh insights into the organization of the mammalian ERAD interaction network and the functions of its components.
Cole R.J.,University of British Columbia
Building Research and Information | Year: 2011
A workshop held at the 3rd International Holcim Forum, Reinventing Construction, in Mexico City, April 14-17, 2010, explored the social and organizational interplay amongst and between different stakeholders to deliver environmental change. Various common issues evident during the presentations and breakout sessions included the importance of developing comprehensive, context-specific approaches and identifying and acting to a multitude of perspectives and interests or concerns. It was identified that national leaders have yet to achieve concerted and collective international agreement on the targets and measures to curb global GHG emission. While manifest directly and indirectly in terms of resource depletion, degradation of ecosystems and climate change, current environmental issues have their roots in human activity. The understanding of the body of knowledge on innovation along with its underlying policies and practices can provide insights into both change and motivation.
Sarai M.,University of British Columbia
The Cochrane database of systematic reviews | Year: 2013
Patients have been given magnesium to treat or prevent alcohol withdrawal syndrome (AWS). Evidence to support this practice is limited, and is often based on the controversial link between hypomagnesaemia and AWS. To assess the effects of magnesium for the prevention or treatment of AWS in hospitalised adults. We searched the Cochrane Drugs and Alcohol Group Register of Controlled Trials (August 2012), PubMed (from 1966 to August 2012 ), EMBASE (from 1988 to August 2012), CINAHL (from 1982 to March 2010), Web of Science (1965 to August 2012). We also carried out Internet searches. Randomised or quasi-randomised trials of magnesium for hospitalised adults with, or at risk for, acute alcohol withdrawal. Two review authors independently extracted data with a standardised data extraction form, contacting the correspondence investigator if the necessary information was not available in the reports. Dichotomous outcomes were analysed by calculating the risk ratio (RR) for each trial, with the uncertainty in each result expressed with a 95% confidence interval (CI). Continuous outcomes were to be analysed by calculating the standardised mean difference (SMD) with 95% CI. For outcomes assessed by scales we compared and pooled the mean score differences from the end of treatment to baseline (post minus pre) in the experimental and control groups. Four trials involving 317 people met the inclusion criteria. Three trials studied oral magnesium, with doses ranging from 12.5 mmol/day to 20 mmol/day. One trial studied parenteral magnesium (16.24 mEq q6h for 24 hours). Each trial demonstrated a high risk of bias in at least one domain. There was significant clinical and methodological variation between trials.We found no study that measured all of the identified primary outcomes and met the objectives of this review. Only one trial measured clinical symptoms of seizure, delirium tremens or components of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score. A single outcome (handgrip strength) in three trials (113 people), was amenable to meta-analysis. There was no significant increase in handgrip strength in the magnesium group (SMD 0.04; 95% CI -0.22 to 0.30). No clinically important changes in adverse events were reported. There is insufficient evidence to determine whether magnesium is beneficial or harmful for the treatment or prevention of alcohol withdrawal syndrome.
Cole R.J.,University of British Columbia
Building Research and Information | Year: 2012
Green building strategies, performance goals, and associated assessment methods currently emphasize the ways and extent that buildings should mitigate global and local resource depletion and environmental degradation. By contrast, the emerging notion of regenerative design and development emphasizes a co-evolutionary, partnered relationship between humans and the natural environment, rather than a managerial one that builds, rather than diminishes, social and natural capitals. Three ideas are addressed. First, understanding the relationship between green, sustainable, and regenerative design and associated assessment frameworks, giving emphasis to how they represent and engage natural systems and processes. Second, characterizing the type of discussions that these three approaches generate amongst the design team and between the design team and its clients in terms of strengthening an understanding of natural systems. Finally, the inherent potential of green, sustainability and regenerative design approaches to create the necessary and timely changes in performance improvements. One of the most significant differences - and central to this discussion - lies in the ways that uncertainty of the long-term outcomes associated with different design decisions are acknowledged and accommodated in design. © 2012 Taylor & Francis.
Johnson J.D.,University of British Columbia
Advances in Experimental Medicine and Biology | Year: 2010
Diabetes occurs when β-cells no longer function properly or have been destroyed. Pancreatic β-cell death by apoptosis contributes significantly in both autoimmune type 1 diabetes and type 2 diabetes. Pancreatic β-cell death can be induced by multiple stresses in both major types of diabetes. There are also several rare forms of diabetes, including Wolcott-Rallison syndrome, Wolfram syndrome, as well as some forms of maturity onset diabetes of the young that are caused by mutations in genes that may play important roles in β-cell survival. The use of islet transplantation as a treatment for diabetes is also limited by excessive β-cell apoptosis. Mechanistic insights into the control of pancreatic β-cell apoptosis are therefore important for the prevention and treatment of diabetes. Indeed, a substantial quantity of research has been dedicated to this area over the past decade. In this chapter, we review the factors that influence the propensity of β-cells to undergo apoptosis and the mechanisms of this programmed cell death in the initiation and progression of diabetes. © Springer Science+Business Media B.V. 2010.
Nielsen T.O.,University of British Columbia |
West R.B.,Stanford University
Journal of Clinical Oncology | Year: 2010
Whereas most solid tumors are characterized by considerable genetic instability and molecular heterogeneity, sarcomas include many subtypes with very specific underlying molecular events driving oncogenesis. Gene expression profiling and other modern techniques have consequently had particular success in identifying the critical biologic pathways active in specific sarcomas, yielding insights which can be translated into useful diagnostic biomarkers. Public availability of data sets and new sequencing-based technologies will accelerate this process. Molecular studies have also identified oncogenic pathways of particular importance in sarcomas which can be targeted by investigational drugs. Examples include histone deacetylases in translocation-associated sarcomas of young adults, Akt/mammalian target of rapamycin in pleomorphic sarcomas, and macrophage colony-stimulating factor in tenosynovial giant cell tumor. Despite challenges in organization and accrual, future clinical trials of sarcomas need to be designed that take into account specific molecular subtypes as distinct diseases. © 2010 by American Society of Clinical Oncology.
Saw J.,University of British Columbia
Catheterization and Cardiovascular Interventions | Year: 2014
Spontaneous coronary artery dissection (SCAD) is under-diagnosed and the true prevalence is underestimated. Unfortunately, SCAD is frequently missed on coronary angiogram since the arterial wall is not imaged with this test. Optical coherence tomography or intravascular ultrasound should be the true gold-standard to diagnose SCAD. Given the elusive angiographic diagnosis of SCAD and the lack of familiarity with angiographic variants of SCAD, a diagnostic algorithm and angiographic classification for SCAD is proposed in this article. © 2013 Wiley Periodicals, Inc.
Pyenson N.D.,University of British Columbia
Paleobiology | Year: 2010
To understand how well fossil assemblages represent original communities, paleoecologists seek comparisons between death assemblages and their source communities. These comparisons have traditionally used nearshore, marine invertebrate assemblages for their logistical ease, high abundance, and comparable census data from living communities. For large marine vertebrates, like cetaceans, measuring their diversity in ocean ecosystems is difficult and expensive. Cetaceans, however, often beach or strand themselves along the coast, and archived data on stranded cetaceans have been recorded, in some areas, over several decades. If the stranding record is interpreted as a death assemblage, then the stranding record may represent a viable alternative for measuring diversity in living communities on directly adjacent coastlines. This study assessed the fidelity of the cetacean stranding record in the eastern North Pacific Ocean. The living community in this region has been studied for over 100 years and, recently, extensive and systematic live transect surveys using ship-based observing platforms have produced a valuable source of live diversity data. Over this same period, the U.S. Marine Mammal Stranding Program has collected and archived a record of cetacean strandings along the U.S. Pacific coastline, providing an ideal death assemblage for comparison. Using fidelity metrics commonly used in marine invertebrate taphonomy, I determined that the stranding record samples the living cetacean community with high fidelity, across fine and coarse taxonomic ranks, and at large geographic scales (>1000 km of coastline). The stranding record is also richer than the live surveys, with live-dead ratios between 1.1 and 1.3. The stranding record recovers similar rank-order relative abundances as live surveys, with statistical significance. Also, I applied sample-based rarefaction methods to generate collector's curves for strandings along the U.S. Pacific Coast to better evaluate the spatiotemporal characteristics of the stranding record. Results indicate that saturation (i.e., sampling >95 assemblage) at species, genus, and family levels occurs in less than five years of sampling, with families accumulating faster than species, and larger geographic regions (i.e., longer coastlines) accumulating taxa the most rapidly. The high fidelity of the stranding record, measured both in richness and by ranked relative abundance, implies that ecological structure from living cetacean communities is recorded in the death assemblage, a finding that parallels marine invertebrate assemblages, though at far larger spatial scales. These results have implications for studying cetacean ecology in both modern and ancient environments: first, these results imply that the stranding record, over sufficiently long time intervals, yields a richer assemblage than using line-transect methods, and faithfully records aspects of community structure; and second, these results imply that geochronologically well-constrained fossil cetacean assemblages might preserve ecologically relevant features of community structure, depending on depositional and taphonomic conditions. © 2010 The Paleontological Society. All rights reserved.
Church M.,University of British Columbia
Progress in Physical Geography | Year: 2010
Modern geomorphology was founded in the nineteenth century as an exercise of historical interpretation of landscapes. After the mid-twentieth century it dominantly became a quest to understand the processes by which landscapes are modified. This focused attention on the measurement of sediment fluxes on synoptic timescales and on a reductionist, Newtonian programme of construction of low-order theories about those fluxes, largely imported from engineering science. The period also saw the emergence of an applied geomorphology. Toward the end of the twentieth century the subject was dramatically transformed by improved technologies for remote sensing and surveying of Earth's surface, the advent of personal computation and of large-scale computation, and important developments of absolute dating techniques. These technical innovations in turn promoted recognition of geomorphology as a 'system science' and facilitated the reintegration of tectonics into geomorphology, opening the way for a renewed consideration of the history of the landscape. Finally, increasing recognition of the dominance of human agency in contemporary modification of Earth's terrestrial surface has become a significant theme. Important influences on the continuing development of the subject will include the search for physically sound laws for material fluxes; reconciling geomorphological information and process representations across spatial and temporal scales, in both observation and theory; comprehending complexity in geomorphological processes and landform histories; incorporating the geomorphological role of living organisms, particularly micro-organisms; understanding the role of climate in geomorphology, both in the contemporary changing climate and in the long term; and fully admitting the now dominant role of humans as geomorphic agents. Geomorphology is simultaneously developing in diverse directions: on one hand, it is becoming a more rigorous geophysical science - a significant part of a larger earth science discipline; on another, it is becoming more concerned with human social and economic values, with environmental change, conservation ethics, with the human impact on environment, and with issues of social justice and equity. © The Author(s) 2010.
Chang S.E.,University of British Columbia
Disasters | Year: 2010
This paper provides a framework for assessing empirical patterns of urban disaster recovery through the use of statistical indicators. Such a framework is needed to develop systematic knowledge on how cities recover from disasters. The proposed framework addresses such issues as defining recovery, filtering out exogenous influences unrelated to the disaster, and making comparisons across disparate areas or events. It is applied to document how Kobe City, Japan, recovered from the catastrophic 1995 earthquake. Findings indicate that while aggregate population regained pre-disaster levels in ten years, population had shifted away from the older urban core. Economic recovery was characterised by a three to four year temporary boost in reconstruction activities, followed by settlement at a level some ten per cent below pre-disaster levels. Other long-term effects included substantial losses of port activity and sectoral shifts toward services and large businesses. These patterns of change and disparity generally accelerated pre-disaster trends. © 2010 The Author(s). Journal compilation © Overseas Development Institute, 2010.
Safier N.,University of British Columbia
ISIS | Year: 2010
Since Bruno Latour's discussion of a Sakhalin island map used by La Pérouse as part of a global network of "immutable mobiles," the commensurability of European and non-European knowledge has become an important issue for historians of science. But recent studies have challenged these dichotomous categories as reductive and inadequate for understanding the fluid nature of identities, their relational origins, and their historically constituted character. Itineraries of knowledge transfer, traced in the wake of objects and individuals, offer a powerful heuristic alternative, bypassing artificial epistemological divides and avoiding the limited scale of national or monolingual frames. Approaches that place undue emphasis either on the omnipotence of the imperial center or the centrality of the colonial periphery see only half the picture. Instead, practices of knowledge collection, codification, elaboration, and dissemination-in European, indigenous, and mixed or hybrid contexts-can be better understood by following their moveable parts, with a keen sensitivity toward non-normative epistemologies and more profound temporal frameworks. © 2010 by The History of Science Society.
Clowes R.M.,University of British Columbia
Canadian Journal of Earth Sciences | Year: 2010
Lithoprobe is Canada's national, collaborative, multidisciplinary, Earth science research project established to develop a comprehensive understanding of the evolution of northern North America. It is regarded internationally as one of the most successful national geoscience projects ever undertaken. Part of Lithoprobe's success derives from its history and organizational structure. A one-year Phase I program (1984-1985) was highly successful. Phases II to V carried the project forward until 2005, when funding terminated. Lithoprobe was organized as a decentralized research network of multidisciplinary scientific studies and collaborating scientists. About 1500 scientific publications were generated. Lithoprobe's legacy also includes economic and social benefits. New and improved understanding of Earth history provides petroleum and mining companies with an enhanced knowledge base. Lithoprobe demonstrated the applicability of high-resolution seismic reflection studies to mineral exploration. Development of a portable seismic refraction recorder and a long-period magnetotelluric system led to technology transfer to Canadian companies. Very high-resolution seismic reflection studies, applied first by Lithoprobe, are proving effective for exploration for uranium deposits in Saskatchewan. In the cratonic areas of Canada, Lithoprobe seismic and magnetotelluric studies have provided significant new information relevant to exploration for diamonds. On the west coast of Canada, Lithoprobe studies provided data and a framework for better understanding the mega-thrust earthquake hazard in the region. Lithoprobe established a highly effective public outreach strategy that involved the print and electronic media as well as material for educational purposes. Unequivocally, Lithoprobe has enhanced the already strong reputation of the Earth sciences in Canada.
Pawlowicz R.,University of British Columbia
Ocean Science | Year: 2010
Salinity determination in seawater has been carried out for almost 30 years using the Practical Salinity Scale 1978. However, the numerical value of so-called practical salinity, computed from electrical conductivity, differs slightly from the true or absolute salinity, defined as the mass of dissolved solids per unit mass of seawater. The difference arises because more recent knowledge about the composition of seawater is not reflected in the definition of practical salinity, which was chosen to maintain historical continuity with previous measures, and because of spatial and temporal variations in the relative composition of seawater. Accounting for these spatial variations in density calculations requires the calculation of a correction factor δSA, which is known to range from 0 to 0.03 g kg-1 in the world oceans. Here a mathematical model relating compositional perturbations to δSA is developed, by combining a chemical model for the composition of seawater with a mathematical model for predicting the conductivity of multi-component aqueous solutions. Model calculations for this estimate of δSA, denoted δSRsoln, generally agree with estimates of δSA based on fits to direct density measurements, denoted δSRdens, and show that biogeochemical perturbations affect conductivity only weakly. However, small systematic differences between model and density-based estimates remain. These may arise for several reasons, including uncertainty about the biogeochemical processes involved in the increase in Total Alkalinity in the North Pacific, uncertainty in the carbon content of IAPSO standard seawater, and uncertainty about the haline contraction coefficient for the constituents involved in biogeochemical processes. This model may then be important in constraining these processes, as well as in future efforts to improve parameterizations for δSA. © Author(s) 2010.
Bakker K.,University of British Columbia
Annual Review of Environment and Resources | Year: 2014
This article reviews the literature relevant to market environmentalism in the water sector, focusing on five themes: the privatization of resource ownership and management, the commercialization of resource management organizations, the environmental valuation and pricing of resources, the marketization of trading and exchange mechanisms, and the liberalization of governance. For each dimension, the discussion addresses a topic of contemporary academic interest (and policy and political relevance): privatization and protest, the contradictions of commercialization, the distinction between environmental valuation and commodification, the multiplication of modes ofmarketization, and the limits to the liberalization of environmental governance. Specific attention is given to unresolved questions and tensions in the debate over market environmentalism, particularly the tension between human rights and environmental rights and among state, market, and community roles in water management. Copyright © 2014 by Annual Reviews. All rights reserved.
Yatham L.N.,University of British Columbia
Molecular Psychiatry | Year: 2015
Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry (‘0-weeks’ group) or (ii) at 24 weeks after entry (‘24-weeks’ group) or (iii) continuation of risperidone or olanzapine for the full duration of the study (‘52-weeks’ group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.Molecular Psychiatry advance online publication, 13 October 2015; doi:10.1038/mp.2015.158. © 2015 Macmillan Publishers Limited
Scott D.W.,Center for Lymphoid Cancer |
Gascoyne R.D.,Center for Lymphoid Cancer |
Gascoyne R.D.,University of British Columbia
Nature Reviews Cancer | Year: 2014
B cell lymphomas are cancers that arise from cells that depend on numerous highly orchestrated interactions with immune and stromal cells in the course of normal development. Despite the recent focus on dissecting the genetic aberrations within cancer cells, it has been increasingly recognized that tumour cells retain a range of dependence on interactions with the non-malignant cells and stromal elements that constitute the tumour microenvironment. A fundamental understanding of these interactions gives insight into the pathogenesis of most B cell lymphomas and, moreover, identifies novel therapeutic opportunities for targeting oncogenic pathways, both now and in the future. © 2014 Macmillan Publishers Limited.
MacDonald-Jankowski D.S.,University of British Columbia
Dentomaxillofacial Radiology | Year: 2010
Objectives: The aims of the review were to evaluate the principal clinical and conventional radiographic features of orthokeratinized odontogenic cyst (OOC) by systematic review (SR), and to compare the frequency of OOC between four global groups. Methods: The databases searched were the PubMed interface of MEDLINE and LILACS. Only those reports of OOCs that occurred in a consecutive series of OOCs in the reporting authors' caseload were considered. Results: 37 reports on 36 case series were included in the SR. OOC affected males twice as frequently and the mandible almost 2.5 times as frequently. Although the mean age at first presentation was 35 years, the largest proportion of cases first presented in the third decade for the Western, East Asian and Latin American global groups. Seven reports included details of at least one clinical finding. 11 reported case series included at least 1 radiological feature. All OOCs were radiolucent, 93% were unilocular and 68% were associated with unerupted teeth. 28% of the reported case series included follow up. 4% of OCC recurred and all of these were in the Western global group. Conclusions: Although one feature of OOCs is that they are unlikely to recur, some do. Not only is there a lack of long-term follow up of large series with long-term outcomes of OOC, but there is a paucity of clinical and radiological details of OOC at initial presentation. Dentomaxillofacial Radiology (2010) 39, 455-467. Copyright © 2010 The British Institute of Radiology.
Fang N.N.,University of British Columbia
Nature Cell Biology | Year: 2014
The heat-shock response is a complex cellular program that induces major changes in protein translation, folding and degradation to alleviate toxicity caused by protein misfolding. Although heat shock has been widely used to study proteostasis, it remained unclear how misfolded proteins are targeted for proteolysis in these conditions. We found that Rsp5 and its mammalian homologue Nedd4 are important E3 ligases responsible for the increased ubiquitylation induced by heat stress. We determined that Rsp5 ubiquitylates mainly cytosolic misfolded proteins upon heat shock for proteasome degradation. We found that ubiquitylation of heat-induced substrates requires the Hsp40 co-chaperone Ydj1 that is further associated with Rsp5 upon heat shock. In addition, ubiquitylation is also promoted by PY Rsp5-binding motifs found primarily in the structured regions of stress-induced substrates, which can act as heat-induced degrons. Our results support a bipartite recognition mechanism combining direct and chaperone-dependent ubiquitylation of misfolded cytosolic proteins by Rsp5. © 2014 Nature Publishing Group
Voss C.,University of British Columbia
Journal of physical activity & health | Year: 2013
Parental behavior is an important correlate of child health. The aim of this study was to investigate the association between perceived parental physical activity (PA) and schoolchildren's aerobic fitness. English schoolchildren's (n = 4029, 54% boys, 10.0-15.9 yrs) fitness was assessed by 20 m shuttle run test and categorized using criterion-referenced standards. Parental PA was reported by the child. Boys and girls were more likely to be fit (OR 1.4, 95% CI 1.1-1.8; OR 1.5, 95% CI 1.1-2.0; respectively) if at least 1 parent was perceived as active compared with when neither parents were. Girls were even more likely to be fit (OR 1.8, 95% CI 1.2-2.8) if both parents were active. Associations between parental PA and child fitness were generally stronger when parent and child were of the same gender, although girls with active fathers were more likely (OR 2.5, 95% CI 1.7-3.7) to be fit compared with inactive fathers. Schoolchildren perceiving at least 1 parent as active are more likely to meet health-related fitness standards. Underlying mechanisms remain elusive, but same-gender associations suggest that social rather than genetic factors are of greater importance. Targeting parental PA or at least perceptions of parental PA should be given consideration in interventions aiming to improve child health.
Ritland K.,University of British Columbia
Tree Genetics and Genomes | Year: 2012
Conifers are evolutionarily distant from angiosperms, separated by 300 million years of evolution. The genomes of coniferous species are very large, among the largest of any nonpolyploid plant species. Their genomes are characterized by reduced evolutionary rate for coding genes, accumulation of noncoding DNA, and evolutionarily distance from angiosperms. I highlight both the advantages and disadvantages for conifers as model organism for genomics. With advances of new high-throughput sequencing technologies, we are at a watershed in conifer genomics. © 2012 Springer-Verlag.
Schoof C.,University of British Columbia
Journal of Fluid Mechanics | Year: 2012
We examine the stability of two-dimensional marine ice sheets in steady state. The dynamics of marine ice sheets is described by a viscous thin-film model with two Stefan-type boundary conditions at the moving boundary or 'grounding line' that marks the transition from grounded to floating ice. One of these boundary conditions constrains ice thickness to be at a local critical value for flotation, which depends on depth to bedrock at the grounding line. The other condition sets ice flux as a function of ice thickness at the grounding line. Depending on the shape of the bedrock, multiple equilibria may be possible. Using a linear stability analysis, we confirm a long-standing heuristic argument that asserts that the stability of these equilibria is determined by a simple mass balance consideration. If an advance in the grounding line away from its steady-state position leads to a net mass gain, the steady state is unstable, and stable otherwise. This also confirms that grounding lines can only be stable in positions where bedrock slopes downwards sufficiently steeply. © 2012 Cambridge University Press.
Sigmund K.,University of Vienna |
Sigmund K.,International Institute For Applied Systems Analysis |
De Silva H.,Vienna University of Economics and Business |
Traulsen A.,Max Planck Institute for Evolutionary Biology |
Hauert C.,University of British Columbia
Nature | Year: 2010
Theoretical and empirical research highlights the role of punishment in promoting collaborative efforts. However, both the emergence and the stability of costly punishment are problematic issues. It is not clear how punishers can invade a society of defectors by social learning or natural selection, or how second-order free-riders (who contribute to the joint effort but not to the sanctions) can be prevented from drifting into a coercion-based regime and subverting cooperation. Here we compare the prevailing model of peer-punishment with pool-punishment, which consists in committing resources, before the collaborative effort, to prepare sanctions against free-riders. Pool-punishment facilitates the sanctioning of second-order free-riders, because these are exposed even if everyone contributes to the common good. In the absence of such second-order punishment, peer-punishers do better than pool-punishers; but with second-order punishment, the situation is reversed. Efficiency is traded for stability. Neither other-regarding tendencies or preferences for reciprocity and equity, nor group selection or prescriptions from higher authorities, are necessary for the emergence and stability of rudimentary forms of sanctioning institutions regulating common pool resources and enforcing collaborative efforts. © 2010 Macmillan Publishers Limited. All rights reserved.
Lee A.Y.,University of British Columbia
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2010
Thromboembolism is a common, complex, and costly complication in patients with cancer. Management has changed significantly in the past decade, but remains firmly dependent on the use of anticoagulants. Low-molecular-weight heparin is the preferred anticoagulant for prevention and treatment, although its limitations open opportunities for newer oral antithrombotic agents to further simplify therapy. Multiple clinical questions remain, and research is focusing on identifying high-risk patients who might benefit from primary thromboprophylaxis, treatment options for those with established or recurrent thrombosis, and the potential antineoplastic effects of anticoagulants. Risk-assessment models, targeted prophylaxis, anticoagulant dose escalation for treatment, and ongoing research studying the interaction of coagulation activation in malignancy may offer improved outcomes for oncology patients.
Henrich J.,University of British Columbia
Science | Year: 2014
People in wheat-cultivating areas of China are more individualistic and analytical than those in rice-cultivating areas.
Cullen W.R.,University of British Columbia
Chemical Research in Toxicology | Year: 2014
The bioconversion of inorganic arsenic to methylated metabolites affects the tissue distribution and retention of arsenic and its actions as a toxicant or carcinogen. Although enzymes that catalyze the methylation of arsenicals have been identified in all branches of the tree of life, fundamental questions persist about the chemical processes that underlie reactions that methylate this metalloid. Here, several reaction schemes for arsenic methylation are considered to encourage careful consideration of the chemical plausibility of these schemes. © 2014 American Chemical Society.
Sadownik L.A.,University of British Columbia
International Journal of Women's Health | Year: 2014
Chronic vulvar pain or discomfort for which no obvious etiology can be found, ie, vulvodynia, can affect up to 16% of women. It may affect girls and women across all age groups and ethnicities. Vulvodynia is a significant burden to society, the health care system, the affected woman, and her intimate partner. The etiology is multifactorial and may involve local injury or inflammation, and peripheral and or central sensitization of the nervous system. An approach to the diagnosis and management of a woman presenting with chronic vulvar pain should address the biological, psychological, and social/interpersonal factors that contribute to her illness. The gynecologist has a key role in excluding other causes for vulvar pain, screening for psychosexual and pelvic floor dysfunction, and collaborating with other health care providers to manage a woman's pain. An important component of treatment is patient education regarding the pathogenesis of the pain and the negative impact of experiencing pain on a woman's overall quality of life. An individualized, holistic, and often multidisciplinary approach is needed to effectively manage the woman's pain and pain-related distress. © 2014 Sadownik.
Hungr O.,University of British Columbia |
Leroueil S.,Laval University |
Picarelli L.,The Second University of Naples
Landslides | Year: 2014
The goal of this article is to revise several aspects of the well-known classification of landslides, developed by Varnes (1978). The primary recommendation is to modify the definition of landslide-forming materials, to provide compatibility with accepted geotechnical and geological terminology of rocks and soils. Other, less important modifications of the classification system are suggested, resulting from recent developments of the landslide science. The modified Varnes classification of landslides has 32 landslide types, each of which is backed by a formal definition. The definitions should facilitate backward compatibility of the system as well as possible translation to other languages. Complex landslides are not included as a separate category type, but composite types can be constructed by the user of the classification by combining two or more type names, if advantageous. © 2013 Springer-Verlag Berlin Heidelberg.
Prescott C.E.,University of British Columbia
Biogeochemistry | Year: 2010
Key recent developments in litter decomposition research are reviewed. Long-term inter-site experiments indicate that temperature and moisture influence early rates of litter decomposition primarily by determining the plants present, suggesting that climate change effects will be small unless they alter the plant forms present. Thresholds may exist at which single factors control decay rate. Litter decomposes faster where the litter type naturally occurs. Elevated CO2 concentrations have little effect on litter decomposition rates. Plant tissues are not decay-resistant; it is microbial and biochemical transformations of materials into novel recalcitrant compounds rather than selective preservation of recalcitrant compounds that creates stable organic matter. Altering single characteristics of litter will not substantially alter decomposition rates. Nitrogen addition frequently leads to greater stabilization into humus through a combination of chemical reactions and enzyme inhibition. To sequester more C in soil, we need to consider not how to slow decomposition, but rather how to divert more litter into humus through microbial and chemical reactions rather than allowing it to decompose. The optimal strategy is to have litter transformed into humic substances and then chemically or physically protected in mineral soil. Adding N through fertilization and N-fixing plants is a feasible means of stimulating humification. © 2010 Springer Science+Business Media B.V.
Fortin P.M.,University of British Columbia
Cochrane database of systematic reviews (Online) | Year: 2013
Wegener's granulomatosis (WG) is a necrotizing small-vessel vasculitis that can affect any organ in the body but mainly affects the upper and lower respiratory tract, the kidneys, joints, skin and eyes. The current mainstay of remission induction therapy is systemic corticosteroids in combination with oral daily cyclophosphamide (CYC) which induces remission in 75% to 100% of cases. Although standard therapy is effective in inducing partial or complete remission, 50% of complete remissions are followed by at least one relapse. This is an update of a review first published in 2009. To determine if intravenous immunoglobulin (IVIg) adjuvant therapy provides a therapeutic advantage over and above treatment with systemic corticosteroids in combination with immunosuppressants for the treatment of WG. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and CENTRAL (2012, Issue 11). Trial databases were searched by the TSC for details of ongoing and unpublished studies. No date or language restrictions were applied. Randomized controlled trials (RCTs), or quasi RCTs, or randomized cross-over trials. Participants had to be adults with a confirmed diagnosis of WG. Two authors independently extracted data and assessed trial quality. Relative risk was used to analyze dichotomous variables, and mean difference (MD) was used to analyze continuous variables. We included one RCT with 34 participants who were randomly assigned to receive IVIg or placebo once daily in addition to azathioprine and prednisolone for remission maintenance. There were no significant differences between adjuvant IVIg and adjuvant placebo in mortality, serious adverse events, time to relapse, open-label rescue therapy, and infection rates. The fall in disease activity score, derived from patient-reported symptoms, was slightly greater in the IVIg group than in the placebo group at one month (MD 2.30; 95% Confidence interval (CI) 1.12 to 3.48, P < 0.01) and three months (MD 1.80; 95% CI 0.35 to 3.25, P = 0.01). There was a significant increase in total adverse events in the IVIg group (relative risk (RR) 3.50; 95% CI 1.44 to 8.48, P < 0.01). There is insufficient evidence from one RCT that IVIg adjuvant therapy provides a therapeutic advantage compared with the combination of steroids and immunosuppressants for patients with WG. Given the high cost of IVIg (one dose at 2 g/kg for a 70 kg patient = $8,400), it should be limited to treat WG in the context of a well conducted RCT powered to detect patient-relevant outcomes.
Jahanfar S.,University of British Columbia
Cochrane database of systematic reviews (Online) | Year: 2013
Mastitis can be caused by ineffective positioning of the baby at the breast or restricted feeding. Infective mastitis is commonly caused by Staphylococcus aureus. The prevalence of mastitis in breastfeeding women may reach 33%. Effective milk removal, pain medication and antibiotic therapy have been the mainstays of treatment. This review aims to examine the effectiveness of antibiotic therapies in relieving symptoms for breastfeeding women with mastitis with or without laboratory investigation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2012), contacted investigators and other content experts known to us for unpublished trials and scanned the reference lists of retrieved articles. We selected randomised controlled trials (RCTs) and quasi-RCTs comparing the effectiveness of various types of antibiotic therapies or antibiotic therapy versus alternative therapies for the treatment of mastitis. Two review authors independently assessed trial quality and extracted data. When in dispute, we consulted a third author. Two trials met the inclusion criteria. One small trial (n = 25) compared amoxicillin with cephradine and found no significant difference between the two antibiotics in terms of symptom relief and abscess formation. Another, older study compared breast emptying alone as 'supportive therapy' versus antibiotic therapy plus supportive therapy, and no therapy. The findings of the latter study suggested faster clearance of symptoms for women using antibiotics, although the study design was problematic. There is insufficient evidence to confirm or refute the effectiveness of antibiotic therapy for the treatment of lactational mastitis. There is an urgent need to conduct high-quality, double-blinded RCTs to determine whether antibiotics should be used in this common postpartum condition.
Jahanfar S.,University of British Columbia
Cochrane database of systematic reviews (Online) | Year: 2013
Domestic violence during pregnancy is a major public health concern. This preventable risk factor threatens both the mother and baby. Routine perinatal care visits offer opportunities for healthcare professionals to screen and refer abused women for effective interventions. It is, however, not clear which interventions best serve mothers during pregnancy and postpartum to ensure their safety. To examine the effectiveness and safety of interventions in preventing or reducing domestic violence against pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (19 June 2012), scanned bibliographies of published studies and corresponded with investigators. We included randomised controlled trials (RCTs) including cluster-randomised trials, and quasi-randomised controlled trials (e.g. where there was alternate allocation) investigating the effect of interventions in preventing or reducing domestic violence during pregnancy. Two review authors independently assessed trial quality and extracted data. We included nine trials with a total of 2391 women; however, for most outcomes very few studies contributed data and results were predominantly based on findings from single studies. There was evidence from one study that the total number of women reporting episodes of partner violence during pregnancy, and in the postpartum period was reduced for women receiving a psychological therapy intervention (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.48 to 0.88). There were few statistically significant differences between intervention and control groups for depression during pregnancy and the postnatal period. Only one study reported findings for neonatal outcomes such as preterm delivery and birthweight, and there were no clinically significant differences between groups. None of the studies reported results for other secondary outcomes: Apgar score less than seven at one minute and five minutes, stillbirth, neonatal death, miscarriage, maternal mortality, antepartum haemorrhage, and placental abruption. There is insufficient evidence to assess the effectiveness of interventions for domestic violence on pregnancy outcomes. There is a need for high-quality, RCTs with adequate statistical power to determine whether intervention programs prevent or reduce domestic violence episodes during pregnancy, or have any effect on maternal and neonatal mortality and morbidity outcomes.
Jahanfar S.,University of British Columbia
Cochrane database of systematic reviews (Online) | Year: 2013
Maternal caffeine consumption during pregnancy may have adverse effects on fetal, neonatal and maternal outcomes. This review investigates the effects of restricting caffeine intake by mothers on fetal, neonatal and pregnancy outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2012), scanned bibliographies of published studies and corresponded with investigators. Randomised controlled trials (RCTs) including quasi-RCTs investigating the effect of caffeine and/or supplementary caffeine versus restricted caffeine intake or placebo on pregnancy outcomes. Two review authors independently assessed trial quality and extracted data. Two studies met the inclusion criteria but only one contributed data for the prespecified outcomes. Caffeinated instant coffee (568 women) was compared with decaffeinated instant coffee (629 women) and it was found that reducing the caffeine intake of regular coffee drinkers (3+ cups/day) during the second and third trimester by an average of 182 mg/day did not affect birthweight or length of gestation. There is insufficient evidence to confirm or refute the effectiveness of caffeine avoidance on birthweight or other pregnancy outcomes. There is a need to conduct high-quality, double-blinded RCTs to determine whether caffeine has any effect on pregnancy outcome.
Hewitt I.J.,University of British Columbia
Earth and Planetary Science Letters | Year: 2010
Upwelling regions of the mantle can undergo partial melting as a result of decompression. Many models for the dynamics of these regions have largely ignored the actual melting process or have prescribed a uniform melting rate proportional to the upwelling velocity. This paper uses a simple model for an upwelling column to calculate the melting rate from conservation principles. The model rock comprises two chemical components, and is assumed to be in thermodynamic equilibrium. For idealized linear phase constraints the melting rate can be calculated analytically, and is found to be proportional to the average upwelling velocity of both the matrix and melt.A secondary aim is to discuss reactive instabilities; the model predicts that the one dimensional state will be linearly stable, whereas previous models have suggested that reactive infiltration instability should occur. This is argued to be a result of the 'background' melting rate which has not usually been fully accounted for, but which has a stabilizing effect. The model here can also be applied to a column in which some melt is already present, and in that case it does exhibit a channeling instability. It is concluded that accounting for melt production consistently in mid-ocean ridge models is important when assessing the likely modes of melt transport. © 2010 Elsevier B.V.
Novak M.D.,University of British Columbia
Agricultural and Forest Meteorology | Year: 2010
Despite a long history of application to bare soils drying by evaporation, the implications of the coupled heat and moisture transfer theory of Philip and de Vries for temperature and moisture regimes near the soil surface have not been fully described, either because grid resolutions used within the soil in numerical implementations were inadequate and/or research objectives were focussed elsewhere. In this paper, a finite-element numerical simulation of heat and moisture regimes using the original theory of Philip and de Vries is applied to a bare silt-loam soil drying during a 10-d rain-free period that occurred at the end of a 66-d field study at Agassiz, British Columbia. The unique aspect of the simulation is that the grid resolution is more than adequate to correctly determine the reported location, magnitude, and shape of the subsurface evaporation zone that develops during daytime for many of the days and corresponding effects on surface energy balance components and soil temperature and moisture. © 2010 Elsevier B.V.
Herrmann F.J.,University of British Columbia
Geophysics | Year: 2010
Many seismic exploration techniques rely on the collection of massive data volumes that are subsequently mined for information during processing. Although this approach has been extremely successful in the past, current efforts toward higher-resolution images in increasingly complicated regions of the earth continue to reveal fundamental shortcomings in our workflows. Chiefly among these is the so-called "curse of dimensionality" exemplified by Nyquist's sampling criterion, which disproportionately strains current acquisition and processing systems as the size and desired resolution of our survey areas continue to increase. We offer an alternative sampling method leveraging recent insights from compressive sensing toward seismic acquisition and processing for data that are traditionally considered to be undersampled. The main outcome of this approach is a new technology where acquisition and processing related costs are no longer determined by overly stringent sampling criteria, such asNyquist. At the heart of our approach lies randomized incoherent sampling that breaks subsampling related interferences by turning them into harmless noise, which we subsequently remove by promoting transform-domain sparsity. Now, costs no longer grow significantly with resolution and dimensionality of the survey area, but instead depend only on transform-domain sparsity. Our contribution is twofold. First, we demonstrate by means of carefully designed numerical experiments that compressive sensing can successfully be adapted to seismic exploration. Second, we show that accurate recovery can be accomplished for compressively sampled data volumes sizes that exceed the size of conventional transform-domain data volumes by only a small factor. Because compressive sensing combines transformation and encoding by a single linear encoding step, this technology is directly applicable to acquisition and to dimensionality reduction during processing. In either case, sampling, storage, and processing costs scale with transform-domain sparsity. We illustrate this principle by means of number of case studies. © 2010 Society of Exploration Geophysicists.
Cairns J.A.,University of British Columbia
Canadian Journal of Cardiology | Year: 2013
Current practice guidelines recommend oral anticoagulant therapy for most patients with nonvalvular atrial fibrillation with more than a low risk of stroke. Although warfarin is very effective and the risk of major bleeding is acceptable, the use of the drug is challenging for patients and physicians. The 3 novel oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban, have been shown to be either noninferior orsuperior to warfarin for the prevention of stroke and/or systemic embolism and their rates of major bleeding are no greater than warfarin. They are much easier for patients to use and for physicians to manage. Except for certain situations in which the NOACs have not been evaluated or some feature of warfarin is preferable, clinical guidelines generally recommend a preference for a NOAC over warfarin when oral anticoagulation is indicated. Although the NOACs have many similarities in their advantageous pharmacokinetic and pharmacodynamic characteristics, there are a number of difference between them with regard to particular patient characteristics (eg, age≥ 75 years, renal dysfunction, coronary artery disease, venous thromboembolism, risk of bleeding, prior stroke and/or transient ischemic attack, side effects, dose regimens, and cost-effectiveness). These differences are outlined and discussed in terms of their potential relevance in deciding among the 3 available NOACs for stroke prevention in atrial fibrillation. © 2013 Canadian Cardiovascular Society.
Clarke L.A.,University of British Columbia
Rheumatology | Year: 2011
The mucopolysaccharidoses (MPSs) are a series of rare genetic disorders in which progressive bone and joint disease represents a key source of morbidity for patients. The recent introduction of enzyme replacement therapy for many of the MPSs has led to a need for increased physician awareness of these rare conditions in order to ensure that treatment is initiated at a time that leads to optimal benefit for patients. In addition, the current experiences of the clinical responsiveness of patient's symptoms to enzyme replacement approaches have also fuelled an interest in the development of alternative and adjunctive therapeutic approaches directed particularly to the rheumatological aspects of disease. Understanding the underlying pathogenesis of the MPSs is a key element for advancements in both of these areas. This review highlights the current knowledge underlying the pathophysiology of disease symptoms in the MPSs and underscores the importance and role of pathogenic cascades. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
Wong T.,University of British Columbia
The Cochrane database of systematic reviews | Year: 2013
Health professionals frequently recommend fever treatment regimens for children that either combine paracetamol and ibuprofen or alternate them. However, there is uncertainty about whether these regimens are better than the use of single agents, and about the adverse effect profile of combination regimens. To assess the effects and side effects of combining paracetamol and ibuprofen, or alternating them on consecutive treatments, compared with monotherapy for treating fever in children. In September 2013, we searched Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and International Pharmaceutical Abstracts (2009-2011). We included randomized controlled trials comparing alternating or combined paracetamol and ibuprofen regimens with monotherapy in children with fever. One review author and two assistants independently screened the searches and applied inclusion criteria. Two authors assessed risk of bias and graded the evidence independently. We conducted separate analyses for different comparison groups (combined therapy versus monotherapy, alternating therapy versus monotherapy, combined therapy versus alternating therapy). Six studies, enrolling 915 participants, are included.Compared to giving a single antipyretic alone, giving combined paracetamol and ibuprofen to febrile children can result in a lower mean temperature at one hour after treatment (MD -0.27 °Celsius, 95% CI -0.45 to -0.08, two trials, 163 participants, moderate quality evidence). If no further antipyretics are given, combined treatment probably also results in a lower mean temperature at four hours (MD -0.70 °Celsius, 95% CI -1.05 to -0.35, two trials, 196 participants, moderate quality evidence), and in fewer children remaining or becoming febrile for at least four hours after treatment (RR 0.08, 95% CI 0.02 to 0.42, two trials, 196 participants, moderate quality evidence). Only one trial assessed a measure of child discomfort (fever associated symptoms at 24 hours and 48 hours), but did not find a significant difference in this measure between the treatment regimens (one trial, 156 participants, evidence quality not graded).In practice, caregivers are often advised to initially give a single agent (paracetamol or ibuprofen), and then give a further dose of the alternative if the child's fever fails to resolve or recurs. Giving alternating treatment in this way may result in a lower mean temperature at one hour after the second dose (MD -0.60 °Celsius, 95% CI -0.94 to -0.26, two trials, 78 participants, low quality evidence), and may also result in fewer children remaining or becoming febrile for up to three hours after it is given (RR 0.25, 95% CI 0.11 to 0.55, two trials, 109 participants, low quality evidence). One trial assessed child discomfort (mean pain scores at 24, 48 and 72 hours), finding that these mean scores were lower, with alternating therapy, despite fewer doses of antipyretic being given overall (one trial, 480 participants, low quality evidence)Only one small trial compared alternating therapy with combined therapy. No statistically significant differences were seen in mean temperature, or the number of febrile children at one, four or six hours (one trial, 40 participants, very low quality evidence).There were no serious adverse events in the trials that were directly attributed to the medications used. There is some evidence that both alternating and combined antipyretic therapy may be more effective at reducing temperatures than monotherapy alone. However, the evidence for improvements in measures of child discomfort remains inconclusive. There is insufficient evidence to know which of combined or alternating therapy might be more beneficial.Future research needs to measure child discomfort using standardized tools, and assess the safety of combined and alternating antipyretic therapy.
Hollenhorst P.C.,Indiana University |
McIntosh L.P.,University of British Columbia |
Graves B.J.,University of Utah |
Graves B.J.,Howard Hughes Medical Institute
Annual Review of Biochemistry | Year: 2011
ETS proteins are a group of evolutionarily related, DNA-binding transcriptional factors. These proteins direct gene expression in diverse normal and disease states by binding to specific promoters and enhancers and facilitating assembly of other components of the transcriptional machinery. The highly conserved DNA-binding ETS domain defines the family and is responsible for specific recognition of a common sequence motif, 5′-GGA(A/T)-3′. Attaining specificity for biological regulation in such a family is thus a conundrum. We present the current knowledge of routes to functional diversity and DNA binding specificity, including divergent properties of the conserved ETS and PNT domains, the involvement of flanking structured and unstructured regions appended to these dynamic domains, posttranslational modifications, and protein partnerships with other DNA-binding proteins and coregulators. The review emphasizes recent advances from biochemical and biophysical approaches, as well as insights from genomic studies that detect ETS-factor occupancy in living cells. © 2011 by Annual Reviews. All rights reserved.
Stewart I.D.,University of British Columbia
International Journal of Climatology | Year: 2011
In the modern era of urban climatology, much emphasis has been placed on observing and documenting heat island magnitudes in cities around the world. Urban climate literature consequently boasts a remarkable accumulation of observational heat island studies. Through time, however, methodologists have raised concerns about the authenticity of these studies, especially regarding the measurement, definition and reporting of heat island magnitudes. This paper substantiates these concerns through a systematic review and scientific critique of heat island literature from the period 1950-2007. The review uses nine criteria of experimental design and communication to critically assess methodological quality in a sample of 190 heat island studies. Results of this assessment are discouraging: the mean quality score of the sample is just 50 percent, and nearly half of all urban heat island magnitudes reported in the sample are judged to be scientifically indefensible. Two areas of universal weakness in the literature sample are controlled measurement and openness of method: one-half of the sample studies fail to sufficiently control the confounding effects of weather, relief or time on reported 'urban' heat island magnitudes, and three-quarters fail to communicate basic metadata regarding instrumentation and field site characteristics. A large proportion of observational heat island literature is therefore compromised by poor scientific practice. This paper concludes with recommendations for improving method and communication in heat island studies through better scrutiny of findings and more rigorous reporting of primary research. © 2010 Royal Meteorological Society.
Smith D.R.,University of British Columbia
Briefings in Functional Genomics | Year: 2013
GenBank is bursting with eukaryotic RNA sequencing (RNA-Seq) results. These data are transforming our view of nuclear transcriptional architecture, butmany scientists are ignoring a major component of the data: mitochondrialand chloroplast-derived sequences. Indeed, organelle transcripts typically represent a significant proportion of the reads generated from eukaryotic RNA-Seq experiments. Here, I argue that these data are an excellent and untapped resource for investigating many aspects of organelle function and evolution. © The Author 2013. Published by Oxford University Press. All rights reserved.
Freeman H.J.,University of British Columbia
World Journal of Gastroenterology | Year: 2010
Celiac disease has been reported in up to 2% of some European populations. A similar risk has been identified in the America and Australia where immigration of Europeans has occurred. Moreover, an increasing number of celiac disease patients are being identified in many Asian countries, including China and India. Finally, celiac disease has also been detected in Asian immigrants and their descendants to other countries, such as Canada. Within these so-called "general" celiac populations, however, there are specific high risk groups that have an even higher prevalence of celiac disease. Indeed, the single most important risk factor for celiac disease is having a first-degree relative with already-defined celiac disease, particularly a sibling. A rate up to 20% or more has been noted. Risk is even greater if a specific family has 2 siblings affected, particularly if a male carries the human leukocyte antigen-DQ2. Both structural changes in the small bowel architecture occur along with functional changes in permeability, even in asymptomatic first-degree relatives. Even if celiac disease is not evident, the risk of other autoimmune disorders seems significantly increased in first-degree relatives as well as intestinal lymphoma. Identification of celiac disease is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated. © 2010 Baishideng.
Bakker K.,University of British Columbia
Environment and Planning D: Society and Space | Year: 2013
This paper presents a historical analysis of the evolution of the World Bank's policies on urban water supply networks, from 1960 to the late 1980s. The analysis frames urban water supply as an attempt (contested and incomplete) to extend the biopolitical power of developmental states. I argue that the World Bank's agenda was predicated on a set of contradictions (and an untenable public/private binary) that contributed to the emergence of 'state failure' arguments by the late 1980s. This perspective enables critical refl ection on the historical origins of the concept of 'state failure', and on contemporary debates over urbanization, infrastructure, and development. © 2013 Pion and its Licensors.
Agranovich V.M.,University of Texas at Dallas |
Agranovich V.M.,Russian Academy of Sciences |
Gartstein Y.N.,University of Texas at Dallas |
Litinskaya M.,University of British Columbia
Chemical Reviews | Year: 2011
The hybrid resonant organic-inorganic nanostructures for optoelectronic applications are examined. The probability of Förster resonant energy transfer from an excited molecule to another molecule is proportional to the overlap of the fluorescence spectrum of the donor and the absorption spectrum of the acceptor, these spectra being determined in the absence of the donor acceptor interaction. The dependence of energy transfer on the distance between components of the nanostructure strongly depends on its geometry and is different for quantum wells, wires, and dots. The UV light-emitting InGaN QW is spaced from the blue-light-emitting poly(9,9-dioctylfluorene-co-9,9-di(4- methoxy)phenyl-fluorene) film by GaN cap layers of variable thickness. Energetic alignment is needed to maximize the resonant coupling between the inorganic and organic excitations. The energy-transfer-based hybrids are expected to be more interface quality tolerant and not suffer from low charge carrier mobilities in the organic component.
Ritland K.,University of British Columbia
Molecular Ecology | Year: 2011
The genus Aquilegia consists of 60-70 perennial plant species widely distributed throughout the northern hemisphere. Its flowers have a delicate and ornamental appearance that makes them a favourite of gardeners. In this genus, adaptive radiations for both floral and vegetative traits have occurred. These adaptive radiations, and the key phylogenetic placement of Aquilegia between Arabidopsis and rice, make this genus a 'model system' for plant evolution (Kramer 2009). In this issue, Castellanos (2011) use a marker-based method to infer heritability for floral and vegetative traits in two Aquilegia species. Layered on top of this are estimates of the strength of natural selection. This novel joint estimation of heritability and selection in the wild showed that vegetative traits, compared to floral traits, have the highest evolutionarily potential. Evolutionary potential is the most important quantity to measure in wild populations. It combines inheritance and strength of selection and predicts the potential for populations to adapt to changing environments. The combination of molecular techniques with species in natural environments makes this work a model for molecular ecological investigations. © 2011 Blackwell Publishing Ltd.
Peck J.,University of British Columbia
Environment and Planning A | Year: 2013
Karl Polanyi has been an influential but also somewhat elusive figure in economic geography. Best known for his evocative notion of social embeddedness, it is perhaps fitting that Polanyi's presence has been more metaphorical than substantive. The paper asks what a more engaged Polanyian economic geography might look like. Focusing on methodological affinities, a response is developed in terms of a commitment to the substantivist (as opposed to formal) analysis of actually existing economic formations, together with a more purposive embrace of institutionalism, holism, and comparativism.
Peck J.,University of British Columbia
Environment and Planning A | Year: 2013
The paper provides an introduction to a theme issue devoted to the influence-and the potential-of the work of Karl Polanyi in the field of economic geography. Polanyi has been an inspirational figure in the heterodox field of 'socioeconomics', where the inseparability of the economic and the social is taken to be axiomatic. He has also made recurrent appearances in economic geography since the early 1990s, as a progenitor of the 'networks and embeddedness' approach and in his role as a prescient critic of market fundamentalism. But the potential of Polanyian approaches in economic geography has only been fitfully explored. In this context, the contributions to this theme issue make the case for a more sustained-but also open, critical, and creative-engagement with Polanyi's legacy.
Hall J.G.,University of British Columbia
American Journal of Medical Genetics, Part A | Year: 2013
In a review of 2,300 cases of arthrogryposis collected over the last 35 years, 33 cases of maternal uterine structural anomalies were identified (1.3%). These cases of arthrogryposis represent a very heterogeneous group of types of arthrogryposis. Over half of individuals affected with arthrogryposis demonstrated asymmetry and some responded to removal of constraint, 29 of the 33 cases of arthrogryposis whose mother had a uterine structural anomaly could be identified as having a specific recognizable type of arthrogryposis. Only two cases (0.08%) had primarily proximal contractures that returned to almost normal function within 1 year. Craniofacial asymmetry was the most striking finding in these two cases. A quarter of cases had ruptured membranes between 32 and 36 weeks and either oligohydramnios or prematurity. The pregnancy histories of the mothers with uterine structural anomalies were typical in having infertility, multiple miscarriages, and stillbirths. The finding of only two cases which are likely to have multiple congenital contractures on the basis of uterine constraint suggests that it is a very rare primary cause of arthrogryposis. © 2012 Wiley Periodicals, Inc.
Lesk C.,McGill University |
Rowhani P.,University of Sussex |
Ramankutty N.,McGill University |
Ramankutty N.,University of British Columbia
Nature | Year: 2016
In recent years, several extreme weather disasters have partially or completely damaged regional crop production. While detailed regional accounts of the effects of extreme weather disasters exist, the global scale effects of droughts, floods and extreme temperature on crop production are yet to be quantified. Here we estimate for the first time, to our knowledge, national cereal production losses across the globe resulting from reported extreme weather disasters during 1964-2007. We show that droughts and extreme heat significantly reduced national cereal production by 9-10%, whereas our analysis could not identify an effect from floods and extreme cold in the national data. Analysing the underlying processes, we find that production losses due to droughts were associated with a reduction in both harvested area and yields, whereas extreme heat mainly decreased cereal yields. Furthermore, the results highlight ∼7% greater production damage from more recent droughts and 8-11% more damage in developed countries than in developing ones. Our findings may help to guide agricultural priorities in international disaster risk reduction and adaptation efforts. © 2016 Macmillan Publishers Limited. All rights reserved.
Puyat J.H.,University of British Columbia
Journal of Immigrant and Minority Health | Year: 2013
The association between social support and mental health across immigrant groups were examined in this study. A population-based sample was extracted from a 2009/10 Canadian community health survey. Self-reported mood or anxiety disorders and a standardized social support scale were used as outcome and explanatory variables. The association between these variables was measured using logistic regression controlling for sex, age, marital status, education, self-rated health and perceived stress. Stratified analyses were performed to test if the strength of association differed by immigrant status. In comparison with individuals who had moderate levels of social support, individuals with low social support had higher odds of reporting mental disorders and this association appeared strongest among recent immigrants. Using the same comparison group, individuals with high social support had lower odds of reporting mental disorders and this association appeared stronger among long-term immigrants. Findings were discussed within the context of immigration stress and acculturation strategies. © 2012 Springer Science+Business Media, LLC.
Aslani N.,University of British Columbia
Hernia | Year: 2010
Purpose: To determine the best surgical approach for the open repair of primary umbilical hernias. Methods: Studies were identified through searching MEDLINE, EMBASE, and the Cochrane database, as well as hand-searching references. Randomized controlled trials (RCTs) and observational studies comparing mesh to suture repair for primary umbilical hernias published between January 1965 and October 2009 were included. Data regarding the recurrence rate, complications, number of subjects, length of follow-up, size of hernia, and type of mesh were extracted. Log odds ratios were calculated and weighed by the Mantel-Haenszel method to obtain a pooled estimate with 95% confidence interval (CI). A fixed effects model was used. Results: Three RCTs and ten observational studies were identified. The pooled odds ratio (OR) for RCTs was 0.09 in favor of mesh (95% CI 0.02-0.39). The pooled OR for observational studies was 0.40 in favor of mesh (95% CI 0.21-0.75). There was no difference in complication rates between mesh and tissue repair in RCTs or observational studies. Conclusions: The use of mesh in umbilical hernia repair results in decreased recurrence and similar wound complications rates compared to tissue repair for primary umbilical hernias. © 2010 Springer-Verlag.
Oka A.,Research in Motion |
Lampe L.,University of British Columbia
IEEE Journal on Selected Areas in Communications | Year: 2010
Wireless Sensor Networks are well suited for tracking targets carrying RFID tags in indoor environments. Tracking based on the received signal strength indication (RSSI) is by far the cheapest and simplest option, but suffers from secular biases due to effects of multi-path, occlusions and decalibration, as well as large unbiased errors due to measurement noise. We propose a novel algorithm that solves these problems in a distributed, scalable and power-efficient manner. Firstly, our proposal includes a tandem incremental estimator that learns and tracks the radio environment of the network, and provides this knowledge for the use of the tracking algorithm, which eliminates the secular biases due to radio occlusions etc. Secondly, we reduce the unbiased tracking error by exploiting the co-dependencies in the motion of several targets (as in crowds or herds) via a fully distributed and tractable particle filter. We thereby extract a significant 'diversity gain' while still allowing the network to scale seamlessly to a large tracking area. In particular, we avoid the pitfalls of network congestion and severely shortened battery lifetimes that plague procedures based on the joint multi-target probability density. © 2010 IEEE.
Bakker K.,University of British Columbia
Science | Year: 2012
New strategies for analyzing water security have the potential to improve coordination and generate synergies between researchers, policy-makers, and practitioners.
Seto K.C.,Yale University |
Ramankutty N.,University of British Columbia
Science | Year: 2016
Global societies are becoming increasingly urban. This shift toward urban living is changing our relationship with food, including how we shop and what we buy, as well as ideas about sanitation and freshness. Achieving food security in an era of rapid urbanization will require considerably more understanding about how urban and food systems are intertwined. Here we discuss some potential understudied linkages that are ripe for further examination.
Balevi B.,University of British Columbia
Community Dentistry and Oral Epidemiology | Year: 2011
Background and objective: Visually distinguishing oral cancer from noncancerous oral lesions is problematic. Currently, commercial diagnostic devices are being marketed to dentists as effective screening devices to use in general practice. The purpose of this study is to evaluate the probabilistic performance of VELscope®, Oral CDx® and toludine blue staining as clinical adjunctive diagnostic procedures in routine screening for oral cancer in dental practice. Materials and methods: Sensitivity and specificity information for each device was taken from the literature. The positive predictive value (PPV) and false positive rate, based on three clinical screening scenario, were calculated using Bayes' Theorem. Results: Under three clinical scenarios (screening the general population, screening only adults (≥40 years) and screening adults (≥40 years) that present with intra-oral visible lesions), VELscope produced the highest PPV's of 1.27%, 2.53% and 8.11%, respectively. This indicates a false positive rate of between 91.89% and 98.73%. Conclusion: VELscope, OralCDx and toludine blue staining have high false positive rates when they are used to screen routinely for oral cancer. It would be inefficient to allocate scarce healthcare resources to the routine use of these devices for oral cancer screening. These devices may be beneficial in opportunistic screening programmes or in cancer referral clinics when the pretest probability of oral cancer is likely to be above 10%. Further research is needed to determine at which pretest probabilities these adjunctive diagnostic devices would be cost-beneficial for the screening of oral cancer. © 2010 John Wiley & Sons A/S.
Rabkin S.W.,University of British Columbia
Metabolic Syndrome and Related Disorders | Year: 2014
Epicardial fat (epicardial adipose tissue, EAT) has been implicated in the pathogenesis of coronary artery disease (CAD). The objective of this study was to examine the relationship between EAT and generalized obesity, central or visceral adipose tissue (VAT), and the components of the metabolic syndrome - systolic blood pressure (SBP), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and fasting blood glucose (FBG) - that are linked to CAD. A systematic review of the literature, following meta-analysis guidelines, was conducted until May, 2013, using the search strategy "Obesity" OR "abdominal obesity" OR "metabolic syndrome" OR "metabolic syndrome X" AND "epicardial fat". Thirty-eight studies fulfilled the criteria. There was a highly significant (P<0.00001) correlation between EAT and body mass index (BMI), waist circumference (WC), or VAT. The correlation between EAT and VAT was significantly (P<0.0001) greater than the correlation between EAT and WC, which in turn was significantly greater than the correlation between EAT and BMI. Overall, EAT was 7.5±0.1 mm in thickness in the metabolic syndrome (n=427) compared to 4.0±0.1 mm in controls (n=301). EAT correlated significantly (P<0.0001) with SBP, TGs, HDL, and FBG, but the strength of the association was less than one-half of the relationship of EAT to indices of obesity. The results of multivariate analysis were less consistent but show a relationship between EAT and metabolic syndrome independent of BMI. In summary, the very strong correlation between EAT and VAT suggests a relationship between these two adipose tissue depots. Measurement of EAT can be useful to indicate VAT. Whereas EAT correlates significantly with each of the components of the metabolic syndrome - SBP, TGs, HDL, or FBG - the magnitude of the relationship is considerably and significantly less than the relationship of EAT to BMI. These data show the strong relationship between EAT and BMI but especially with WC and VAT. They also demonstrate the smaller magnitude of the association of EAT with standard coronary risk factors, related to the metabolic syndrome, and suggest that the unique features of this adipose tissue warrant detailed investigation. © Mary Ann Liebert, Inc.
Rabkin S.W.,University of British Columbia
Journal of Alzheimer's Disease | Year: 2012
Arterial stiffness constitutes a reduction in the ability of large arteries to readily accommodate the increase in blood ejected from the heart during systole. Propagation of the pulse wave or pulse wave velocity (PWV) is a relatively simple, non-invasive, and reproducible method to determine arterial stiffness. There is mounting evidence that consistently implicates arterial stiffness in the pathogenesis of impaired cognitive function and dementia in the elderly. This paper summarizes this evidence. First, the majority (85%) of the twelve studies comprising over 6,000 individuals found a significant association between increased vascular stiffness and cognitive impairment in multivariate analysis after adjusting for age, educational level, and other factors that influence cognition. Second, higher pulse wave velocity, adjusted for age and other factors, was associated with a greater amount of white matter hyperintensities on brain imaging, indicating cerebral small-vessel disease. Third, studies consistently indicate that higher PWV is a significant predictor of subsequent cognitive decline. Fourth, some data support the proposition that arterial stiffness (PWV) increases progressively from persons with normal cognitive function to those with mild cognitive impairment, to Alzheimer's disease, and then to vascular dementia. Fifth, there is some suggestion that antihypertensive drugs that have a more favorable effect to reduce vascular stiffness are more likely to reduce the occurrence of cognitive impairment. Taken together, these data suggest that artery stiffness may be a useful clinical tool to detect individuals at risk for cognitive impairment and dementia of the elderly. © 2012 - IOS Press and the authors. All rights reserved.
Gilbert B.,University of British Columbia
Journal of Ecology | Year: 2012
1. Several ecological theories predict that species coexist by exploiting different resource niches, and therefore, more diverse communities should have greater resource uptake. Supporting evidence, however, is equivocal. Species with similar competitive abilities are predicted to coexist with little niche differentiation, suggesting that communities containing more functionally redundant species may be more diverse but with little impact on resource use. Likewise, high rates of seed dispersal often increase diversity, but the effect of this diversity on resource uptake is unknown. 2.I incorporate resource competition into a metacommunity model where communities differ in regional diversity and also in the dispersal and niche overlap (functional redundancy) of their constituent species. In this model, each species within the metacommunity is the optimal competitor in one or more patches, and the patches are linked by dispersal. 3. The model predicts that niche overlap and dispersal have similar and synergistic effects on local diversity, but opposite effects on resource use. Increasing niche overlap and dispersal causes an increase in local diversity to a critical point, after which local diversity crashes. However, increasing dispersal invariably decreases resource use, whereas increasing niche overlap increases resource use. Increasing the regional species pool causes the only consistently positive relationship between local diversity and function but becomes saturated at a local species richness of 2-3 species. 4. Synthesis. The distinct mechanisms that drive diversity in local communities can have different and even opposing effects on resource use. Understanding how dispersal and niche overlap structure diversity is critical to predicting the relationship between diversity and resource use. Distinguishing between these mechanisms should be a priority when attempting to understand the causes and consequences of diversity. © 2011 The Author. Journal of Ecology © 2011 British Ecological Society.
Attwell D.,University College London |
Buchan A.M.,University of Oxford |
Charpak S.,University of Paris Descartes |
Lauritzen M.,Copenhagen University |
And 2 more authors.
Nature | Year: 2010
Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now recognized that neurotransmitter-mediated signalling has a key role in regulating cerebral blood flow, that much of this control is mediated by astrocytes, that oxygen modulates blood flow regulation, and that blood flow may be controlled by capillaries as well as by arterioles. These conceptual shifts in our understanding of cerebral blood flow control have important implications for the development of new therapeutic approaches. © 2010 Macmillan Publishers Limited. All rights reserved.
Loewen C.J.R.,University of British Columbia
F1000 Biology Reports | Year: 2012
The lipid phosphatidic acid is an important metabolic intermediate in the biosynthesis of lipids in all eukaryotic cells, but it is even more than that. Phosphatidic acid is emerging as a lipid that is both composer and conductor, where in addition to its role as biosynthetic precursor (composer) it is also a potent signaling molecule (conductor) that integrates membrane biogenesis with nutrient sensing and cell growth. This article discusses recent advances in yeast that give praise for phosphatidic acid as one of life's conductors. © 2012 Faculty of 1000 Ltd.
Jafarnejad S.M.,University of British Columbia
Cancer metastasis reviews | Year: 2012
The INhibitor of Growth (ING) family is an evolutionarily conserved set of proteins, implicated in suppression of initiation and progression of cancers in various tissues. They promote cell cycle arrest, cellular senescence and apoptosis, participate in stress responses, regulate DNA replication and DNA damage responses, and inhibit cancer cell migration, invasion, and angiogenesis of the tumors. At the molecular level, ING proteins are believed to participate in chromatin remodeling and transcriptional regulation of their target genes. However, the best known function of ING proteins is their cooperation with p53 tumor suppressor protein in tumor suppression. All major isoforms of ING family members can promote the transactivition of p53 and the majority of them are shown to directly interact with p53. In addition, ING proteins are thought to interact with and modulate the function of auxiliary members of p53 pathway, such as MDM2, ARF , p300, and p21, indicating their widespread involvement in the regulation and function of this prominent tumor suppressor pathway. It seems that p53 pathway is the main mechanism by which ING proteins exert their functions. Nevertheless, regulation of other pathways which are not relevant to p53, yet important for tumorigenesis such as TGF-β and NF-κB, by ING proteins is also observed. This review summarizes the current understanding of the mutual interactions and cooperation between different members of ING family with p53 pathway and implications of this cooperation in the suppression of cancer initiation and progression.
Krishnamurthy V.,University of British Columbia
IEEE Transactions on Information Theory | Year: 2011
We show that the optimal decision policy for several types of Bayesian sequential detection problems has a threshold switching curve structure on the space of posterior distributions. This is established by using lattice programming and stochastic orders in a partially observed Markov decision process (POMDP) framework. A stochastic gradient algorithm is presented to estimate the optimal linear approximation to this threshold curve. We illustrate these results by first considering quickest time detection with phase-type distributed change time and a variance stopping penalty. Then it is proved that the threshold switching curve also arises in several other Bayesian decision problems such as quickest transient detection, exponential delay (risk-sensitive) penalties, stopping time problems in social learning, and multi-agent scheduling in a changing world. Using Blackwell dominance, it is shown that for dynamic decision making problems, the optimal decision policy is lower bounded by a myopic policy. Finally, it is shown how the achievable cost of the optimal decision policy varies with change time distribution by imposing a partial order on transition matrices. © 2011 IEEE.
Vellend M.,University of British Columbia
Quarterly Review of Biology | Year: 2010
Community ecology is often perceived as a "mess," given the seemingly vast number of processes that can underlie the many patterns of interest, and the apparent uniqueness of each study system. However, at the most general level, patterns in the composition and diversity of species-the subjectmatter of community ecology-are influenced by only four classes of process: selection, drift, speciation, and dispersal Selection represents deterministic fitness differences among species, drift represents stochastic changes in species abundance, speciation creates new species, and dispersal is the movement of organisms across space. All theoretical and conceptual models in community ecology can be understood with respect to their emphasis on these four processes. Empirical evidence exists for all of these processes and many of their interactions, with a predominance of studies on selection. Organizing the material of community ecology according to this framework can clarify the essential similarities and differences among the many conceptual and theoretical approaches to the discipline, and it can also allow for the articulation of a very general theory of community dynamics: species are added to communities via speciation and dispersal, and the relative abundances of these species are then shaped by drift and selection, as well as ongoing dispersal, to drive community dynamics. Copyright © 2010 by The University of Chicago Press. All rights reserved.
Richerson P.J.,University of California at Davis |
Boydb R.,University of California at Los Angeles |
Henrichc J.,University of British Columbia
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010
The use of socially learned information (culture) is central to human adaptations. We investigate the hypothesis that the process of cultural evolution has played an active, leading role in the evolution of genes. Culture normally evolves more rapidly than genes, creating novel environments that expose genes to new selective pressures. Many human genes that have been shown to be under recent or current selection are changing as a result of new environments created by cultural innovations. Some changed in response to the development of agricultural subsistence systems in the Early and Middle Holocene. Alleles coding for adaptations to diets rich in plant starch (e.g., amylase copy number) and to epidemic diseases evolved as human populations expanded (e.g., sickle cell and G6PD deficiency alleles that provide protection against malaria). Large-scale scans using patterns of linkage disequilibrium to detect recent selection suggest that many more genes evolved in response to agriculture. Genetic change in response to the novel social environment of contemporary modern societies is also likely to be occurring. The functional effects of most of the alleles under selection during the last 10,000 years are currently unknown. Also unknown is the role of paleoenvironmental change in regulating the tempo of hominin evolution. Although the full extent of culture-driven gene-culture coevolution is thus far unknown for the deeper history of the human lineage, theory and some evidence suggest that such effects were profound. Genomic methods promise to have a major impact on our understanding of gene-culture coevolution over the span of hominin evolutionary history.
Dunham Y.,University of California at Merced |
Baron A.S.,University of British Columbia |
Carey S.,Harvard University
Child Development | Year: 2011
Three experiments (total N=140) tested the hypothesis that 5-year-old children's membership in randomly assigned "minimal" groups would be sufficient to induce intergroup bias. Children were randomly assigned to groups and engaged in tasks involving judgments of unfamiliar in-group or out-group children. Despite an absence of information regarding the relative status of groups or any competitive context, in-group preferences were observed on explicit and implicit measures of attitude and resource allocation (Experiment 1), behavioral attribution, and expectations of reciprocity, with preferences persisting when groups were not described via a noun label (Experiment 2). In addition, children systematically distorted incoming information by preferentially encoding positive information about in-group members (Experiment 3). Implications for the developmental origins of intergroup bias are discussed. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.
Hammell K.R.W.,University of British Columbia
Disability and Rehabilitation | Year: 2010
Purpose.To highlight research priorities of people with spinal cord injury (SCI), outline the current state of rehabilitation research and suggest potentially fruitful avenues for future inquiry. Method.Commentary. Results.People with SCI identify pain, depression, fatigue, pressure sores, spasticity and the management of bladder and bowel as research priorities. Research reveals multiple interconnections between these secondary problems, all of which negatively impact quality of life (QOL). However, despite a substantial volume of existing research, significant gaps in knowledge remain, duplications of research effort are apparent and few interventions have an adequate evidence base. Issues concerning community participation another research priority have only recently attracted researchers' attention. Conclusions.This commentary contends that research should: focus on issues and outcomes of relevance and importance to people living with SCI; address the complexities of secondary conditions and their inter-relationships; appraise environmental barriers to participation in meaningful living; be designed to identify and inform effective and relevant interventions. Innovative approaches to research partnerships, mixed methods and exploring variables usually omitted from quantitative studies might enhance the likelihood that the complexity of issues facing people living with SCI will be identified and addressed. Moreover, a governing focus on achieving lives experienced as hopeful, purposeful, satisfying and meaningful could contribute to enhancing QOL outcomes following SCI. © 2010 Informa UK Ltd.
Lam C.S.,McGill University |
Lam C.S.,University of British Columbia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013
We search for possible symmetries present in the leptonic mixing data from SU(3) subgroups of order up to 511. Theoretical results based on symmetry are compared with global fits of experimental data in a chi-squared analysis, yielding the following results. There is no longer a group that can produce all the mixing data without a free parameter, but a number of them can accommodate the first or the second column of the mixing matrix. The only group that fits the third column is Δ(150). It predicts sin ¡22θ13=0.11 and sin ¡22θ23=0.94, in good agreement with experimental results. © 2013 American Physical Society.
Berciu M.,University of British Columbia
Physical Review Letters | Year: 2011
We show how few-particle Green's functions can be calculated efficiently for models with nearest-neighbor hopping, for infinite lattices in any dimension. As an example, for one-dimensional spinless fermions with both nearest-neighbor and second-nearest-neighbor interactions, we investigate the ground states for up to 5 fermions. This allows us not only to find the stability region of various bound complexes, but also to infer the phase diagram at small but finite concentrations. © 2011 American Physical Society.
Webber S.,University of British Columbia
Environment and Planning A | Year: 2013
This paper explores some of the perverse effects of climate change adaptation policies and financing in the Republic of Kiribati, a low-lying island nation in the Central Pacific. I examine how encounters between financiers and government officials might produce vulnerability to climate change. I draw throughout from field research conducted in Kiribati, an archetypical 'vulnerable-to-climate-change' place, and a preeminent site for experimentation in climate change adaptation. By discussing several instances where Government of Kiribati elites are required to enact vulnerability in order to secure climate change adaptation financing, I demonstrate that such encounters are performative. This research contributes to theories of performativity in showing that the matrix conditioning and compelling such performative enactments of vulnerability is socionatural, consisting of a collective of climate change impacts, adaptation-finance technocrats, and many others. Thus, I demonstrate that vulnerability is not a latent condition, but, rather, an emergent effect of an assemblage of facts, expert actors, and objects. © 2013 Pion and its Licensors.
Brotto L.A.,University of British Columbia
Journal of Sexual Medicine | Year: 2010
Introduction.: Hypoactive Sexual Desire Disorder (HSDD) is one of two sexual desire disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and is defined by two criteria: A-" persistently or recurrently deficient (or absent) sexual fantasies and desire for sexual activity" and B-" marked distress or interpersonal difficulty." Aim.: This paper reviews the prevalence and correlates of low desire in men and qualitative and quantitative research on the experience of sexual desire in men and women. Methods.: A literature search of Medline, PudMed, and PsychInfo was used to identify any publication on low desire in men. Main Outcome Measure.: The strength of empirical findings was used as a basis for making proposed revisions to the diagnostic criteria for HSDD in men. Results.: The dilemma of whether desire and arousal can be reliably differentiated in men is discussed, and parallels to the literature in women are drawn. Finally, I consider three options for the diagnosis of low desire in men for DSM-5. Option 1 proposes that the DSM-IV-TR name and criteria are preserved for men in DSM-5. Option 2 proposes that the recently proposed criteria for Sexual Interest Arousal Disorder in women are also adopted for men, which would result in one gender-neutral category. Option 3 proposes that the criteria for Sexual Interest Arousal Disorder also be applied to men, with a minor modification to one criterion (i.e., that absent or reduced genital and or nongenital physical changes not be included as a criterion); this diagnosis would then be applied only to men. Conclusions.: The evidence supporting each of these proposals is presented and critiqued. It is concluded that the proposal for DSM-5 should be made on the basis of field testing of new criteria. © 2010 International Society for Sexual Medicine.
Fitzjohn R.G.,University of British Columbia
Methods in Ecology and Evolution | Year: 2012
1. The R package 'diversitree' contains a number of classical and contemporary comparative phylogenetic methods. Key included methods are BiSSE (binary state speciation and extinction), MuSSE (a multistate extension of BiSSE), and QuaSSE (quantitative state speciation and extinction). Diversitree also includes methods for analysing trait evolution and estimating speciation/extinction rates independently. 2. In this note, I describe the features and demonstrate use of the package, using a new method, MuSSE (multistate speciation and extinction), to examine the joint effects of two traits on speciation. 3. Using simulations, I found that MuSSE could reliably detect that a binary trait that affected speciation rates when simultaneously accounting for additional thats that had no effect on speciation rates. 4. Diversitree is an open source and available on the Comprehensive R Archive Network (cran). A tutorial and worked examples can be downloaded from http://www.zoology.ubc.ca/prog/diversitree. Video © 2012 The Authors. Methods in Ecology and Evolution © 2012 British Ecological Society.
Jackson J.K.,University of British Columbia
International journal of nanomedicine | Year: 2011
The objective of this work was to investigate the use of nanocrystalline cellulose (NCC) as a drug delivery excipient. NCC crystallites, prepared by an acid hydrolysis method, were shown to have nanoscopic dimensions and exhibit a high degree of crystallinity. These crystallites bound significant quantities of the water soluble, ionizable drugs tetratcycline and doxorubicin, which were released rapidly over a 1-day period. Cetyl trimethylammonium bromide (CTAB) was bound to the surface of NCC and increased the zeta potential in a concentration-dependent manner from -55 to 0 mV. NCC crystallites with CTAB-modified surfaces bound significant quantities of the hydrophobic anticancer drugs docetaxel, paclitaxel, and etoposide. These drugs were released in a controlled manner over a 2-day period. The NCC-CTAB complexes were found to bind to KU-7 cells, and evidence of cellular uptake was observed.
Warren M.,University of California at San Diego |
Rottler J.,University of British Columbia
Physical Review Letters | Year: 2013
In the glassy state, all materials undergo a process of structural recovery as they age towards equilibrium. The resultant increase of relaxation times tα is frequently described with a sublinear power of the wait time twμ with an apparent aging exponent μ. We show with molecular dynamics simulations of a Lennard-Jones glass former at various temperatures that the observed aging exponent can be strongly influenced by crossover effects from the freshly quenched state at short tw and into the equilibrated state at long tw. The aging behavior on the molecular level is quantitatively reproduced by a coarse-grained continuous time random walk description over the entire range of temperatures and wait times. Our model glass always shows normal aging, tα∼tw, when the observation time window is no longer affected by crossover effects, in agreement with the well-known trap model of aging. © 2013 American Physical Society.
Jackson M.G.,University of California at Santa Barbara |
Jellinek A.M.,University of British Columbia
Geochemistry, Geophysics, Geosystems | Year: 2013
The bulk composition of the silicate portion of the Earth (BSE) has long been assumed to be tied to chondrites, in which refractory, lithophile elements like Sm and Nd exist in chondritic relative abundances. However, the 142Nd/144Nd ratios of modern terrestrial samples are 18 ± 5 ppm higher than the ordinary-chondrite reservoir, and this challenges the traditional BSE model. Here we investigate a hypothesis that this terrestrial 142Nd excess is related to a Sm/Nd ratio 6% higher than chondritic. This Sm/Nd ratio yields a superchondritic 143Nd/ 144Nd (∼0.5130) similar to that identified in the highest 3He/4He mantle reservoir, and we argue that this reservoir represents the BSE composition for lithophile elements. We develop a compositional model for BSE in which the elevated Sm/Nd requires a shift of 143Nd/144Nd from 0.51263 (chondritic) to 0.51300. The new BSE composition is depleted in highly incompatible elements, including K, relative to the chondrite-based BSE, and offers a solution the "missing" 40Ar paradox. This BSE compositional model requires that >83% of the mantle is depleted to form continental crust. It also implies a ∼30% reduction in BSE U, Th and K, and therefore in the current rate of radiogenic heating and, thus, a proportional increase in the heat flow delivered to surface by plate tectonics. We explore thermal history models including effects related to a newly recognized evolution in the style of plate tectonics over Earth history: The lower radiogenic heat production may delay the onset of core convection and dynamo action to as late as 3.5 Gyr. ©2013. American Geophysical Union. All Rights Reserved.
Morshed M.G.,University of British Columbia
Advances in Experimental Medicine and Biology | Year: 2014
Syphilis is a century old sexually transmitted infection transmitted worldwide. WHO reports 12 million new cases that were identified in 1999, with over 90 % of these infections reported from patients from low-income countries. This case number of syphilis is on the rise globally in the Men have sex with Men (MSM) population. Dark field microscopy (DFM) and direct fluorescence assay (DFA) have been used in clinical laboratories for decades to demonstrate Treponema pallidum in acutely infected human tissue and/or body fluids. Molecular technologies allow detecting T. pallidum and also determine drug resistance (by identifying DNA point mutation). It is evident from the published literature that PCR is useful as an adjunct test to DFA and DFM, and is useful in confirming syphilis in genital ulcer, tissue, and other body fluid samples, providing even more sensitive detection algorithm. Serological tests remain the mainstay tests since T. pallidum is nonculturable and also because blood collection is easy. The practice of serological testing is changing rapidly from traditional nontreponemal screening followed by confirmatory treponemal testing to screening by treponemal tests referred to as “Reverse Algorithm” followed by nontreponemal testing to determine active infections. Special and further complex algorithms are essential to deal with complex issues such as neurosyphilis or congenital syphilis. Due to the huge surge of syphilis in developing countries where access to medical care is not optimal, point of care or rapid tests may play an important role. This author took an attempt to summarize the current trend of syphilis diagnosis and challenges from a global perspective. © Springer India 2014.
Kumar U.,University of British Columbia
Endocrine | Year: 2011
The process of homo- and/or heterodimerization of G-protein coupled receptors (GPCRs) and receptor tyrosine kinase (RTK) families are crucial for implicating the fundamental properties of receptor proteins including receptor expression, trafficking, and desensitization as well as signal transduction. The members of GPCR and RTK family constitute largest cell surface receptor proteins and regulate physiological functions of cells in response to external and internal stimuli. Notably, GPCRs and RTKs play major role in regulation of several key cellular functions which are associated with several pathological conditions including cancer biology, neurodegenerative and cardiovascular diseases. The focus of this review is to highlight the recent findings on the possible cross-talk between somatostatin receptors (members of GPCR family) and growth factor receptors like epidermal growth factor receptors (members of RTK family). Furthermore, functional consequences of such an interaction in modulation of signaling pathways linked to pathological conditions specifically in cancer are discussed. © Springer Science+Business Media, LLC 2011.
Clark L.,University of British Columbia
Annals of the New York Academy of Sciences | Year: 2014
The reclassification of gambling disorder within the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) addictions category marks an important step for addiction science. The similarities between gambling disorder and the substance use disorders have been well documented. As gambling is unlikely to exert actively damaging effects on the brain, the cognitive sequelae of gambling disorder may provide insights into addictive vulnerabilities; this idea is critically evaluated in light of recent structural imaging data. The second part of the review analyzes a fundamental question of how a behavior can become addictive in the absence of exogenous drug stimulation. The relative potency of drug and nondrug rewards is considered, alongside evidence that cognitive distortions in the processing of chance (for example, the illusion of control and the gambler's fallacy) may constitute an important added ingredient in gambling. Further understanding of these mechanisms at neural and behavioral levels will be critical for the classification of future behavioral addictions, and I consider the current research data for obesity and binge eating, compulsive shopping, and internet gaming disorder. © 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc.
Rachman S.,University of British Columbia
Behaviour Research and Therapy | Year: 2015
The historical background of the development of behaviour therapy is described. It was based on the prevailing behaviourist psychology and constituted a fundamentally different approach to the causes and treatment of psychological disorders. It had a cold reception and the idea of treating the behaviour of neurotic and other patients was regarded as absurd. The opposition of the medical profession and psychoanalysts is explained. Parallel but different forms of behaviour therapy developed in the US and UK. The infusion of cognitive concepts and procedures generated a merger of behaviour therapy and cognitive therapy, cognitive behaviour therapy (CBT). The strengths and limitations of the early and current approaches are evaluated. © 2014 Elsevier Ltd.
Lachapelle U.,University of British Columbia
Journal of physical activity & health | Year: 2011
Most public transit users walk to and from transit. We analyzed the relationship between transit commuting and objectively measured physical activity. Adults aged 20 to 65 working outside the home (n = 1237) were randomly selected from neighborhoods in Seattle and Baltimore regions. Neighborhoods had high or low median income and high or low mean walkability. Mean daily minutes of accelerometer-measured moderate-intensity physical activity (MPA) were regressed on frequency of commuting by transit and neighborhood walkability, adjusting for demographic factors and enjoyment of physical activity. Interaction terms and stratification were used to assess moderating effect of walkability on the relation between transit commuting and MPA. Associations between transit commuting and self-reported days walked to destinations near home and work were assessed using Chi Square tests. Regardless of neighborhood walkability, those commuting by transit accumulated more MPA (approximately 5 to 10 minutes) and walked more to services and destinations near home and near the workplace than transit nonusers. Enjoyment of physical activity was not associated with more transit commute, nor did it confound the relationships between MPA and commuting. Investments in infrastructure and service to promote commuting by transit could contribute to increased physical activity and improved health.
Donkin J.J.,University of British Columbia |
Vink R.,University of Adelaide
Current Opinion in Neurology | Year: 2010
PURPOSE OF REVIEW: Although a number of factors contribute to the high mortality and morbidity associated with traumatic brain injury (TBI), the development of cerebral edema with brain swelling remains the most significant predictor of outcome. The present review summarizes the most recent advances in the understanding of mechanisms associated with development of posttraumatic cerebral edema, and highlights areas of therapeutic promise. RECENT FINDINGS: Despite the predominance of cytotoxic (or cellular) edema in the first week after traumatic brain injury, brain swelling can only occur with addition of water to the cranial vault from the vasculature. As such, regulation of blood-brain barrier permeability has become a focus of recent research seeking to manage brain edema. Aquaporins, matrix metalloproteinases and vasoactive inflammatory agents have emerged as potential mediators of cerebral edema following traumatic brain injury. In particular, kinins (bradykinins) and tachykinins (substance P) seem to play an active physiological role in modulating blood-brain barrier permeability after trauma. Substance P neurokinin-1 receptor antagonists show particular promise as novel therapeutic agents. SUMMARY: Attenuating blood-brain barrier permeability has become a promising approach to managing brain edema and associated swelling given that increases in cranial water content can only be derived from the vasculature. Inflammation, both classical and neurogenic, offers a number of attractive targets. © 2010 Lippincott Williams & Wilkins.
Gillen D.,University of British Columbia
Journal of Air Transport Management | Year: 2011
This presentation examines the evolution of airport governance from public utility to modern business. I also briefly look at airport regulation and in this context ask the questions, do airports need to be regulated and if so, why? I consider the new thinking on two-sided platforms and examine whether this may be the new way of thinking about governance. In judging governance structures and regulation, I argue that dynamic efficiency has been underemphasized in the debate over privatization and that airline deregulation has been most important in shifting the balance of power between airlines and airports. © 2010 Elsevier Ltd.
Peirce A.,University of British Columbia
Computer Methods in Applied Mechanics and Engineering | Year: 2015
In this paper we describe an implicit level set algorithm (ILSA) (Peirce and Detournay, 2008) suitable for modeling multi-scale behavior in planar hydraulic fractures propagating in three dimensional elastic media. This multi-scale behavior is typically encountered when multiple physical processes compete to determine the location of the fracture free boundary. Instead of having to match the mesh size to the finest active length scale, or having to re-mesh as the dominant length scales change in space and time, the novel ILSA scheme is able to represent the required multi-scale behavior on a relatively coarse rectangular mesh. This is achieved by using the local front velocity to construct, for each point of a set of control points, a mapping that adaptively identifies the dominant length scale at which the appropriate multi-scale universal asymptotic solution needs to be sampled. Finer-scale behavior is captured in a weak sense by integrating the universal asymptotic solution for the fracture width over partially filled tip elements and using these integrals to set the average values of the widths in all tip elements. The ILSA solution shows good agreement with a multi-scale reference solution comprising a radial solution that transitions from viscosity to toughness dominated propagation regimes. The ILSA scheme is also used to model blade-like hydraulic fractures that break through stress barriers located symmetrically with respect to the injection point. For the zero toughness case, the ILSA solution shows close agreement to experimental results. The multi-scale ILSA scheme is also used to provide results when the material toughness KIc is non-zero. In this case different parts of the fracture-free-boundary can be propagating in different regimes. It is hoped that the multi-scale ILSA solutions presented here will form a set of reference results that can be used to benchmark simulators that use a propagation criterion based on only one dissipative process (either toughness or viscosity). The multi-scale ILSA solutions at larger times (for which plane strain conditions develop in vertical cross sections) are compared with and show close agreement to plane strain exact solutions for height-growth and the fracture width in vertical cross sections. This comparison provides some measure of the accuracy of the multi-scale ILSA scheme. The multi-scale ILSA solutions are also used to identify the regimes of applicability of pseudo 3D (P3D) approximate solutions. These ILSA solutions can also be used to design improved P3D models. © 2014 Elsevier B.V.
Smith K.B.,University of British Columbia |
Pukall C.F.,Queens University
Journal of Sexual Medicine | Year: 2014
Introduction: Despite the impact of provoked vulvar pain on women's sexuality and the partnered sexual context in which the pain typically occurs, partners have not been included widely in research. Aims: To examine sexual and relationship functioning of male partners of women with provoked vulvar pain symptoms using a controlled design and to assess the impact of the pain on their relationship. Methods: Fifty male pain partners and 56 male controls completed questionnaires to assess sexual communication, sexual functioning/satisfaction, sexual esteem, relationship adjustment, and psychological health. Participants also completed numeric rating scales to assess the importance of sex to them and the extent to which they felt their relationship matched a satisfying relationship. To assess the relational impact of vulvar pain, pain partners were asked to indicate whether the pain had impacted their relationship, and, if yes, rated this impact. Main Outcome Measures: Main outcome measures included the Dyadic Sexual Communication Scale, the International Index of Erectile Function, the Sexuality Scale, the Dyadic Adjustment Scale, the 12-Item Short-Form Health Survey, and numeric rating scales. Results: Pain partners reported significantly poorer sexual communication and erectile function and less sexual satisfaction compared with controls. They also reported significantly less affectional expression within their relationships and were more likely than controls to report a discrepancy between their relationship and their idea of a satisfying relationship. Almost 73% (n=32/44) of pain partners reported a negative relational impact of vulvar pain. No significant differences in sexual desire, orgasmic function, sexual esteem, relationship satisfaction and consensus, psychological health, or importance of sex were found between groups. Conclusions: Provoked vulvar pain partners appear negatively impacted with regard to some sexual and physical aspects of their relationship. As one of the few controlled studies to investigate partner functioning in the context of provoked vulvar pain, this study has future research implications and supports the involvement of partners in treatment. © 2014 International Society for Sexual Medicine.
Taylor S.,University of British Columbia
Clinical Psychology Review | Year: 2011
The distinction between early versus late onset is important for understanding many different kinds of disorders. In an effort to identify etiologically homogeneous subtypes of obsessive-compulsive disorder (OCD), numerous studies have investigated whether early onset OCD (EO) can be reliably distinguished from a comparatively later onset form of the disorder (LO). The present article presents a systematic review and evaluation of this subtyping scheme, including meta-analyses and re-analyses of raw data. Regarding the latter, latent class analyses of nine datasets, including clinical and community samples, consistently indicated that age-of-onset is not a unimodal phenomena. Evidence suggests that there are two distinguishable groups; EO (mean onset 11. years) and LO (mean onset 23. years). Approximately three-quarters of cases of OCD (76%) were classified as EO. Meta-analyses indicated that EO, compared to LO, is (a) more likely to occur in males, (b) associated with greater OCD global severity and higher prevalence of most types of OC symptoms, (c) more likely to be comorbid with tics and possibly with other putative obsessive-compulsive spectrum disorders, and (d) associated with a greater prevalence of OCD in first-degree relatives. EO and LO were also distinguishable on other psychosocial and biological variables. Overall, results support the view that EO and LO are distinct subtypes of OCD. Comparisons with other, potentially overlapping OCD subtyping schemes are discussed, implications for DSM-V are considered, and important directions for future investigation are proposed. © 2011 Elsevier Ltd.
McCutcheon J.P.,University of Montana |
Keeling P.J.,University of British Columbia
Current Biology | Year: 2014
New work in aphids shows that a nuclear-encoded protein resulting from a horizontal gene transfer is targeted to a bacterial symbiont, further blurring the distinction between organelle and symbiont. © 2014 Elsevier Ltd All rights reserved.
Zhitnitsky A.R.,University of British Columbia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013
We study novel types of contributions to the entropy of the Maxwell system defined on a compact manifold such as a torus. These new terms are not related to the physical propagating photons. Rather, these novel contributions emerge as a result of tunneling events when transitions occur between topologically different but physically identical vacuum winding states. We compute two new (topologically protected) types of contributions to the entropy in this system resulting from this dynamics. The first contribution has a negative sign, expressed in terms of the magnetic susceptibility, and it is similar in spirit to topological entanglement entropy discussed in condensed matter systems. The second contribution with a positive sign results from the emergent degeneracy which occurs when the system is placed into a background of external magnetic field. This degeneracy resembles a similar effect that occurs at θ=π in topological insulators. Based on these computations we claim that the Maxwell system defined on the four torus behaves in many respects as a topologically ordered system. © 2013 American Physical Society.
Lam C.S.,McGill University |
Lam C.S.,University of British Columbia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013
Using the group theory of mixing to examine all finite subgroups of SU(3) with an order less than 512, we found recently that only the group Δ(150) can give rise to a correct reactor angle θ13 of neutrino mixing without any free parameters. It predicts sin â¡22θ13=0.11 and a submaximal atmospheric angle with sinâ¡22θ 23=0.94, in good agreement with experiment. The solar angle θ12, the charge conjugation-parity phase δ, and the neutrino masses mi are left as free parameters. In this article we provide more details of this case and discuss possible gains and losses by introducing right-handed symmetries and/or valons to construct dynamical models. A simple model is discussed where the solar angle agrees with experiment and all its mixing parameters can be obtained from the group Δ(600) by symmetry alone. The promotion of Δ(150) to Δ(600) is, on one hand, analogous to the promotion of S3 to S4 in the presence of tribimaximal mixing, and on the other hand, it is similar to the extension from A4 to S4 in that case. © 2013 American Physical Society.
Malhotra N.,University of British Columbia
Public Health Nutrition | Year: 2013
Objective Despite a rapidly growing economy and rising income levels in India, improvements in child malnutrition have lagged. Data from the most recent National Family Health Survey reveal that the infant and young child feeding (IYCF) practices recommended by the WHO and the Indian Government, including the timely introduction of solid food, are not being followed by a majority of mothers in India. It is puzzling that even among rich households children are not being fed adequately. The present study analyses the socio-economic factors that contribute to this phenomenon, including the role of nutritional information. Design IYCF practices from the latest National Family Health Survey (2005-2006) were analysed. Multivariate logistic regression analyses were performed to establish the determinants of poor feeding practices. The indicators recommended by the WHO were used to assess the IYCF practices. Setting India. Subjects Children (n 9241) aged 6-18 months. Results Wealth was shown to have only a small effect on feeding practices. For children aged 6-8 months, the mother's wealth status was not found to be a significant determinant of sound feeding practices. Strikingly, nutritional advice on infant feeding practices provided by health professionals (including anganwadi workers) was strongly correlated with improved practices across all age groups. Exposure to the media was also found to be a significant determinant. Conclusions Providing appropriate information may be a crucial determinant of sound feeding practices. Efforts to eradicate malnutrition should include the broader goals of improving knowledge related to childhood nutrition and IYCF practices. © The Author 2012.
Won S.G.,University of British Columbia |
Ra C.S.,Kangwon National University
Water Research | Year: 2011
A new real-time control strategy using moving slope changes of oxidation-reduction potential (ORP)- and pH(mV)-time profiles was designed. Its effectiveness was evaluated by operating a farm-scale sequencing batch reactor (SBR) process using the strategy. The working volume of the SBR was 18 m3, and the volumetric loading rate of influent was 1 m3 cycle-1. The SBR process comprised six phases: feeding → anoxic → anaerobic → aerobic → settle → discharge. The anoxic and aerobic phases were controlled by the developed real-time control strategy. The nitrogen break point (NBP) in the pH(mV)-time profile and the nitrate knee point (NKP) in the ORP-time profile were designated as real-time control points for the aerobic and anoxic phases, respectively. Through successful real-time control, the duration of the aerobic and anoxic phases could be optimized and this resulted in very high N removal and a flexible hydraulic retention time. Despite the large variation in the loading rate (0.5-1.8 kg NH4-N m-3 cycle-1) due to influent strength fluctuation, complete removal of NH4-N (100%) was always achieved. The removal efficiencies of soluble nitrogen (NH4-N plus NOx-N), soluble total organic carbon, and soluble chemical oxygen demand were 98%, 90%, and 82%, respectively. Monitoring the ORP and pH(mV) revealed that pH(mV) is a more reliable control parameter than ORP for the real-time control of the oxic phase. In some cases, a false NBP momentarily appeared in the ORP-time profile but was not observed in the pH(mV)-time profile. In contrast, ORP was more the reliable control parameter for NKP detection in the anoxic phase, since the appearance of NKP in the pH(mV)-time profile was sometimes vague. © 2010 Elsevier Ltd.
Milsom W.K.,University of British Columbia
Respiratory Physiology and Neurobiology | Year: 2012
The location (gills, oro-branchial cavity or elsewhere) and orientation (external (water) or internal (blood) sensing) of the receptors involved in reflex changes in each of the different components of the cardiorespiratory response (breathing frequency, breath amplitude, heart rate, systemic vascular resistance) to hypoxia and hypercarbia are highly variable between species of water and air breathing fish. Although not universal, the receptors involved in eliciting changes in heart rate and breathing frequency in response to hypoxia and hypercarbia tend to be restricted exclusively to the gills while those producing increases in breath amplitude are more wide spread, frequently also being found at extrabranchial sites. The distribution of the chemoreceptors sensitive to CO2 in the gills involved in producing ventilatory responses tend to be more restricted than that of the O2-sensitive chemoreceptors and the specific location of the receptors involved in the various components of the cardiorespiratory response can vary from those of the O2-sensitive chemoreceptors. © 2012 Elsevier B.V.
Rachman S.,University of British Columbia
Behaviour Research and Therapy | Year: 2010
Betrayal is the sense of being harmed by the intentional actions or omissions of a trusted person. The most common forms of betrayal are harmful disclosures of confidential information, disloyalty, infidelity, dishonesty. They can be traumatic and cause considerable distress. The effects of betrayal include shock, loss and grief, morbid pre-occupation, damaged self-esteem, self-doubting, anger. Not infrequently they produce life-altering changes. The effects of a catastrophic betrayal are most relevant for anxiety disorders, and OC D and PTSD in particular.Betrayal can cause mental contamination, and the betrayer commonly becomes a source of contamination. In a series of experiments it was demonstrated that feelings of mental contamination can be aroused by imagining unacceptable non-consensual acts. The magnitude of the mental contamination was boosted by the introduction of betrayal themes. Feelings of mental contamination can also be aroused in some 'perpetrators' of non-consensual acts involving betrayal. The psychological significance of acts of betrayal is discussed. © 2009 Elsevier Ltd.
Van Waerbeke L.,University of British Columbia
Monthly Notices of the Royal Astronomical Society | Year: 2010
The potential of cosmic shear to probe cosmology is well recognized and future optical wide field surveys are currently being designed to optimize the return of cosmic shear science. High precision cosmic shear analysis requires high precision photometric redshift. With accurate photometric redshifts, it becomes possible to measure the cosmic magnification on galaxies by galaxies and use it as a probe of cosmology. This type of weak lensing measurement will not use galaxy shapes, instead it will strongly rely on precise photometry and detailed colour information. In this work it is shown that such a measurement would lead to competitive constraints of the cosmological parameters, with a remarkable complementarity with cosmic shear. Future cosmic shear surveys could gain tremendously from magnification measurements as an independent probe of the dark matter distribution leading to a better control of observational and theoretical systematics when combined with shear. © 2009 RAS.
Lamers Y.,University of British Columbia
Annals of Nutrition and Metabolism | Year: 2011
An adequate intake of folate during pregnancy, lactation, and infancy is essential for maternal and child health and normal growth. Higher folate requirements during pregnancy and lactation are difficult to meet by increased intake of folate-rich food products only. Supplementation with folic acid is recommended not only to meet the higher requirements but also to prevent adverse pregnancy outcomes such as neural tube defects (NTDs). In countries that have implemented food fortification with folic acid, the folate intake has raised but does not yet meet the recommended amount for NTD risk reduction. Women's awareness of the need to supplement with folic acid prior to conception shall be raised in all countries. It is under debate whether a high folic acid intake might have metabolic and functional effects in utero and for the infant. Research is needed to investigate potential alternative folate forms for food fortification programs and to test their efficacy in risk reduction of adverse pregnancy outcomes. Breast-fed infants most likely receive sufficient folate. While the folate level of human milk is simulated in infant formula, data are lacking on the bioavailability and effect of folic acid in infants and on whether a tolerable upper intake level should be defined. Copyright © 2011 S. Karger AG, Basel.
McElhaney J.E.,University of British Columbia |
McElhaney J.E.,University of Connecticut
Ageing Research Reviews | Year: 2011
The most profound consequences of immune senescence with respect to public health are the increased susceptibility to influenza and loss of efficacy of the current split-virus influenza vaccines in older adults, which are otherwise very effective in younger populations. Influenza infection is associated with high rates of complicated illness including pneumonia, heart attacks and strokes in the 65+ population. Changes in both innate and adaptive immune function not only converge in the reduced response to vaccination and protection against influenza, but present significant challenges to new vaccine development. In older adults, the goal of vaccination is more realistically targeted to providing clinical protection against disease rather sterilizing immunity. Correlates of clinical protection may not be measured using standard techniques such as antibody titres to predict vaccine efficacy. Further, antibody responses to vaccination as a correlate of protection may fail to detect important changes in cellular immunity and enhanced vaccine-mediated protection against influenza illness in older people. This article will discuss the impact of influenza in older adults, immunologic targets for improved efficacy of the vaccines, and alternative correlates of clinical protection against influenza that are needed for more effective translation of novel vaccination strategies to improved protection against influenza in older adults. © 2010 Elsevier B.V.
Nogueira F.,University of British Columbia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013
In this paper, inspired by the holographic dual of the entanglement entropy, we consider the behavior of extremal, codimension two, spacelike surfaces in the background of three and four dimensional charged boson stars in asymptotically anti-de Sitter spacetime. We find conditions for which families of minimal area surfaces fail to contain the entire bulk spacetime and construct a phase diagram showcasing the transition between regimes. In addition, we use the relation between the star's mass and the central density of the scalar field to argue for a possible instability of such hollow solutions. Finally, we discuss the consequences of our findings for the study of holographic duals of reduced density matrices. © 2013 American Physical Society.
Regehr G.,University of British Columbia
Medical Education | Year: 2010
Context The health professional education community is struggling with a number of issues regarding the place and value of research in the field, including: the role of theory-building versus applied research; the relative value of generalisable versus contextually rich, localised solutions, and the relative value of local versus multi-institutional research. In part, these debates are limited by the fact that the health professional education community has become deeply entrenched in the notion of the physical sciences as presenting a model for 'ideal' research. The resulting emphasis on an 'imperative of proof' in our dominant research approaches has translated poorly to the domain of education, with a resulting denigration of the domain as 'soft' and 'unscientific' and a devaluing of knowledge acquired to date. Similarly, our adoption of the physical sciences''imperative of generalisable simplicity' has created difficulties for our ability to represent well the complexity of the social interactions that shape education and learning at a local level. Methods Using references to the scientific paradigms associated with the physical sciences, this paper will reconsider the place of our current goals for education research in the production and evolution of knowledge within our community, and will explore the implications for enhancing the value of research in health professional education. Conclusions Reorienting education research from its alignment with the imperative of proof to one with an imperative of understanding, and from the imperative of simplicity to an imperative of representing complexity well may enable a shift in research focus away from a problematic search for proofs of simple generalisable solutions to our collective problems, towards the generation of rich understandings of the complex environments in which our collective problems are uniquely embedded. © 2009 Blackwell Publishing Ltd.
Linden W.,University of British Columbia
Psychosomatic Medicine | Year: 2013
Psychological treatments (PTs) are used as adjuncts to cardiac care. This issue of Psychosomatic Medicine provides a meta-analysis by Rutledge et al. () on the effects of PT and cardiac rehabilitation on depression and cardiac outcomes, and the journal recently published a systematic review and meta-regression on a similar topic by Dickens et al. (). This editorial compares the results from these two meta-analyses and discusses the problems associated with combining different types of PT and other treatments, dose-response effects, floor effects, collapsing across outcomes, and therapist qualifications. PTs have mixed but generally positive effects on reducing mortality and cardiac outcomes, but it remains a challenge explaining how such beneficial outcomes can be achieved by relatively small effects on well-being (typical effect sizes: d = 0.2-0.3). Randomized controlled trials are needed on timing of PT, patients with cardiac problems who will benefit most from PT, and the mechanisms by which PT improves cardiac outcomes. Copyright © 2013 by the American Psychosomatic Society.
Sundberg J.,University of British Columbia
Cultural Geographies | Year: 2014
This paper engages my struggles to craft geo-graphs or earth writings that also further broaden political goals of decolonizing the discipline of geography. To this end, I address a body of literature roughly termed 'posthumanism' because it offers powerful tools to identify and critique dualist constructions of nature and culture that work to uphold Eurocentric knowledge and the colonial present. However, I am discomforted by the ways in which geographical engagements with posthumanism tend to reproduce colonial ways of knowing and being by enacting universalizing claims and, consequently, further subordinating other ontologies. Building from this discomfort, I elaborate a critique of geographical-posthumanist engagements. Taking direction from Indigenous and decolonial theorizing, the paper identifies two Eurocentric performances common in posthumanist geographies and analyzes their implications. I then conclude with some thoughts about steps to decolonize geo-graphs. To this end, I take up learnings offered by the Zapatistas. My goal is to foster geographical engagements open to conversing with and walking alongside other epistemic worlds. © The Author(s) 2013.
Luckhaus D.,University of British Columbia
Physical Chemistry Chemical Physics | Year: 2010
The Raman spectrum of formic acid dimer in the OH stretch fundamental range is analysed in terms of a fully coupled vibrational Hamiltonian for the seven most important in-plane degrees of freedom involved in the hydrogen exchange process. The Raman spectrum calculated with potential and polarizability functions obtained from density functional theory reproduces the observed band structure. Wavepacket calculations reveal a remarkably slow hydrogen exchange on the timescale of several ps even at excess energies in the range of 10-15 kJ mol-1. The highly non-statistical process is shown to proceed via adiabatic tunnelling even if excess energy is deposited directly into the reaction coordinate. © 2010 the Owner Societies.
Lee J.,University of British Columbia
PloS one | Year: 2012
Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV(1) and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy "mid-life" volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy "mid-life" volunteers (p<.001). Compared to individuals in the 4(th) quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD.
Raussendorf R.,University of British Columbia
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013
We show, under natural assumptions for qubit systems, that measurement-based quantum computations (MBQCs) which compute a nonlinear Boolean function with a high probability are contextual. The class of contextual MBQCs includes an example which is of practical interest and has a superpolynomial speedup over the best-known classical algorithm, namely, the quantum algorithm that solves the "discrete log" problem. © 2013 American Physical Society.
Kuus M.,University of British Columbia
European Urban and Regional Studies | Year: 2011
This article examines the production of geographical expertise inside the European Union (EU) bureaucracy in Brussels. My question is not what EU policy professionals know, but how they deploy specific knowledge claims as expertise. Drawing from 62 interviews with 42 policy professionals, mostly in Brussels, I focus empirically on one facet of one policy: the eastern direction of the European Neighbourhood Policy and the efforts of the 'new' or post-2004 member states to project regional expertise about the eastern neighbourhood within EU institutions. In conceptual terms, I investigate the intellectual and social technologies by which expert authority is accomplished. The article illuminates the ways in which policy professionals script political space in terms of particular kinds of places to be dealt with by specific agents in specific kinds of ways. The interview material enables me to examine such processes of knowledge production in greater detail than is allowed by the conventional 'big picture' analyses of European integration. © The Author(s) 2011.
Bai T.R.,University of British Columbia
Current Opinion in Allergy and Clinical Immunology | Year: 2010
PURPOSE OF REVIEW: This review focuses on recent findings in relation to potential functional consequences of structural changes in the asthmatic airway. RECENT FINDINGS: Increases in smooth muscle mass have been shown to be an early finding in childhood asthma, related to clinical severity and predictive of greater airflow obstruction. Both hyperplasia and hypertrophy contribute to the increase in smooth muscle mass. A phenotypic shift in the epithelium of asthmatic airways related to stress and injury is suggested by recent data, with likely direct transformation of epithelial cells into mesenchymal cells. Fibrocyte in-migration from the vasculature may be an additional source of increased smooth muscle mass. The increased smooth muscle may contribute to neovascularization via vascular endothelial growth factor. Computed tomography studies continue to show some correlations between wall thickness and airway physiology. Exacerbations are predictive of greater lung function decline and hence remodeling. SUMMARY: On balance, recent evidence continues to show that structural changes contribute to asthma persistence, airflow obstruction, lung function decline, and clinical severity, though there is increased recognition of the heterogeneity of asthma and in some phenotypes inflammatory cell influx or vascular effects may be more important than structural effects. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Levin A.,University of British Columbia |
Stevens P.E.,University of Canterbury
Kidney International | Year: 2014
The 2012 KDIGO Guideline for CKD evaluation, classification, and management has updated the original 2002 KDOQI Guidelines, using newer data and addressing issues raised over the last decade concerning definitions and assessment. This review highlights the key aspects of the CKD guideline, and describes the rationale for specific wording and the scope of the document. A précis of key concepts in each of the five sections of the guideline is presented. The guideline document is intended for general practitioners and nephrologists, and covers CKD evaluation, classification, and management for both adults and children. Throughout the guideline, we have attempted to overtly address areas of controversy or non-consensus, international relevance, and impact on practice and public policy © 2013 International Society of Nephrology.
Gillis J.,University of British Columbia
Nature protocols | Year: 2010
ErmineJ is software for the analysis of functionally interesting patterns in large gene lists drawn from gene expression profiling data or other high-throughput genomics studies. It can be used by biologists with no bioinformatics background to conduct sophisticated analyses of gene sets with multiple methods. It allows users to assess whether microarray data or other gene lists are enriched for a particular pathway or gene class. This protocol provides steps on how to format data files, determine analysis type, create custom gene sets and perform specific analyses-including overrepresentation analysis, genes score resampling and correlation resampling. ErmineJ differs from other methods in providing a rapid, simple and customizable analysis, including high-level visualization through its graphical user interface and scripting tools through its command-line interface, as well as custom gene sets and a variety of statistical methods. The protocol should take approximately 1 h, including (one-time) installation and setup.
Freeman H.J.,University of British Columbia
World Journal of Gastroenterology | Year: 2013
Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent "curative" resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., "tumor budding") should lead to improved staging and clinical care. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.
Xiao B.,Hong Kong Baptist University |
Benbasat I.,University of British Columbia
MIS Quarterly: Management Information Systems | Year: 2011
With the advent of e-commerce, the potential of new Internet technologies to mislead or deceive consumers has increased considerably. This paper extends prior classifications of deception and presents a typology of product-related deceptive information practices that illustrates the various ways in which online merchants can deceive consumers via e-commerce product websites. The typology can be readily used as educational material to promote consumer awareness of deception in e-commerce and as input to establish benchmarks for good business practices for online companies. In addition, the paper develops an integrative model and a set of theory-based propositions addressing why consumers are deceived by the various types of deceptive information practices and what factors contribute to consumer success (or failure) in detecting such deceptions. The model not only enhances our conceptual understanding of the phenomenon of product-based deception and its outcomes in e-commerce but also serves as a foundation for further theoretical and empirical investigations. Moreover, a better understanding of the factors contributing to or inhibiting deception detection can also help government agencies and consumer organizations design more effective solutions to fight online deception.
Glassman J.,University of British Columbia
Geography Compass | Year: 2011
The literature on global production networks (GPNs) has made important contributions to our understanding of globalization, overcoming much of the state-centrism of other kinds of political economic approaches. It has also extended effectively beyond the relatively narrower focus of its predecessors, the global commodity chains and global value chains approaches, to analyze not only the direct process of production but also various social activities that are crucial to the overall process of commodity (and value) production. Yet in spite of opening a potential space for interrogating political processes as integral aspects of production, most work on GPNs has avoided the discussion of political issues that speak to the messiness, contestation, and violence that often accompanies globalization. This article shows that GPN approaches can and should encompass geo-political aspects of the production process that range from labor struggles to inter-state competition and even war. As examples from South Korea show, a geo-political economy approach to GPNs that includes examination of war and geo-politics can extend our understanding of the process of globalization. © 2011 The Author. Geography Compass © 2011 Blackwell Publishing Ltd.
Mackenzie I.R.A.,University of British Columbia |
Frick P.,German Center for Neurodegenerative Diseases |
Neumann M.,German Center for Neurodegenerative Diseases |
Neumann M.,University of Tubingen
Acta Neuropathologica | Year: 2014
An abnormal expansion of a GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72) is the most common genetic abnormality in familial and sporadic FTLD and ALS and the cause in most families where both, FTLD and ALS, are inherited. Pathologically, C9ORF72 expansion cases show a combination of FTLD-TDP and classical ALS with abnormal accumulation of TDP-43 into neuronal and oligodendroglial inclusions consistently seen in the frontal and temporal cortex, hippocampus and pyramidal motor system. In addition, a highly specific feature in C9ORF72 expansion cases is the presence of ubiquitin and p62 positive, but TDP-43 negative neuronal cytoplasmic and intranuclear inclusions. These TDP-43 negative inclusions contain dipeptide-repeat (DPR) proteins generated by unconventional repeat-associated translation of C9ORF72 transcripts with the expanded repeats and are most abundant in the cerebellum, hippocampus and all neocortex regions. Another consistent pathological feature associated with the production of C9ORF72 transcripts with expanded repeats is the formation of nuclear RNA foci that are frequently observed in the frontal cortex, hippocampus and cerebellum. Here, we summarize the complexity and heterogeneity of the neuropathology associated with the C9ORF72 expansion. We discuss implications of the data to the current classification of FTLD and critically review current insights from clinico-pathological correlative studies regarding the fundamental questions as to what processes are required and sufficient to trigger neurodegeneration in C9ORF72 disease pathogenesis. © 2013 Springer-Verlag Berlin Heidelberg.
McFarlane H.E.,University of British Columbia |
McFarlane H.E.,Max Planck Institute of Molecular Plant Physiology |
Doring A.,Max Planck Institute of Molecular Plant Physiology |
Persson S.,Max Planck Institute of Molecular Plant Physiology
Annual Review of Plant Biology | Year: 2014
Plant stature and development are governed by cell proliferation and directed cell growth. These parameters are determined largely by cell wall characteristics. Cellulose microfibrils, composed of hydrogen-bonded β-1,4 glucans, are key components for anisotropic growth in plants. Cellulose is synthesized by plasma membrane-localized cellulose synthase complexes. In higher plants, these complexes are assembled into hexameric rosettes in intracellular compartments and secreted to the plasma membrane. Here, the complexes typically track along cortical microtubules, which may guide cellulose synthesis, until the complexes are inactivated and/or internalized. Determining the regulatory aspects that control the behavior of cellulose synthase complexes is vital to understanding directed cell and plant growth and to tailoring cell wall content for industrial products, including paper, textiles, and fuel. In this review, we summarize and discuss cellulose synthesis and regulatory aspects of the cellulose synthase complex, focusing on Arabidopsis thaliana. Copyright © 2014 by Annual Reviews.
Bell K.,University of British Columbia
Culture, Medicine and Psychiatry | Year: 2012
As numerous scholars have noted, cancer survivorship is often represented in popular discourse as providing an opportunity for a physical, emotional, and spiritual makeover. However, this idea that cancer enables the self to be remade on all levels is also increasingly evoked in the field of psychosocial oncology. Exploring cancer survivorship as a biopolitical phenomenon, I focus on two concepts that have become central to understandings of the disease: the "teachable moment" and "post-traumatic growth." Drawing primarily on representations of cancer survivorship in the clinical literature, I suggest that cancer is increasingly seen to present a unique opportunity to catalyze the patient's physical and psychological development. In this framework, the patient can no longer be relied upon to transform him or herself: this change must be externally driven, with clinicians taking advantage of the trauma that cancer entails to kick-start the patient into action. Broadening my analysis to the concepts of "trauma" and "development" writ large, I go on to suggest that survivorship discourse seems to partake of a larger and relatively recent meta-narrative about development-both individual and societal-and the positive opportunity that trauma is seen to present to stimulate reconstruction on a grand scale. © 2012 The Author(s).
Sehn L.H.,University of British Columbia
Cancer Journal (United States) | Year: 2012
Approximately 25% to 30% of patients with diffuse large B-cell lymphoma (DLBCL) present with limited-stage disease, typically defined as those with nonbulky (<10 cm) Ann Arbor stage I or II disease, without B-symptoms and with sites that can be encompassed within a radiation field. A variety of treatment approaches have been used, which have largely relied on the administration of systemic therapy followed by involved-field radiation therapy (IFRT) to all sites of disease. The use of IFRT has been associated with improved local control, but a significant impact on long-term outcome has not been demonstrated. Although the inclusion of IFRT may allow for an abbreviated course of chemotherapy to be administered, this benefit must be weighed against the potential for radiation-induced acute and delayed toxicity. With the advent of improved systemic therapy, the routine use of IFRT in all patients with limited-stage DLBCL seems no longer justifiable. A tailored-therapy approach, with choice of treatment guided by patient performance status and chemotherapy tolerance, sites of disease involvement, clinical risk factors, and early treatment response would seem rational. Ultimately, greater biologic insight into the heterogeneity of DLBCL will likely result in a personalized treatment approach that relies more on biologic characteristics than stage of disease. © 2012 by Lippincott Williams & Wilkins.
Webb J.,University of British Columbia |
Cribier A.,Charles University
European Heart Journal | Year: 2011
Transcatheter aortic valve implantation (TAVI) is assuming a major role in the routine management of patients with aortic stenosis. Surgical aortic valve replacement is generally accepted to prolong survival, on the basis of historical comparisons and long experience. However, recently percutaneous transarterial TAVI has assumed the position as the only therapy in any aortic stenosis patient group demonstrated to prolong survival in a randomized trial. Arguably, percutaneous TAVI is now the standard of care in symptomatic patients who are not candidates for conventional surgery. On the basis of almost 10 years of experience TAVI also appears to be a reasonable option for some operable, but high-risk patients. Nevertheless considerable work needs to be done before the indications for TAVI are expanded into lower risk groups. We review what is currently known about percutaneous transarterial implantation of the aortic valve. © 2011 The Author.
Daley D.,University of British Columbia
Current Opinion in Allergy and Clinical Immunology | Year: 2014
Purpose of review: Understanding the mechanisms involved in the development of asthma and allergic diseases is expanding, due in part to sequencing advances that have led to the identification of new viral strains such as human rhinovirus strain C (HRV-C) and the human microbiome project. Recent findings: Recent studies have identified new ways in which viral and microbial exposures in early life interact with host genetic background/variants to modify the risk for developing asthma and allergic diseases. Recent research suggests that HRV-C is the main pathogenic agent associated with infant wheeze, hospitalizations and likely the subsequent development of asthma. Pulmonary 3He MRI suggests that HRV infection in early childhood and subsequent immune responses initiate airway remodeling. Numerous studies of the microbiome indicate that intestinal and airway microbiome diversity and composition contribute to the cause of asthma and allergic diseases. Summary: Susceptibility to asthma and allergic diseases is complex and involves genetic variants and environmental exposures (bacteria, viruses, smoking, and pet ownership), alteration of our microbiome and potentially large-scale manipulation of the environment over the past century. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
de Palma A.,Ecole Normale Superieure de Cachan |
Lindsey R.,University of British Columbia
Transportation Research Part C: Emerging Technologies | Year: 2011
This paper reviews the methods and technologies for congestion pricing of roads. Congestion tolls can be implemented at scales ranging from individual lanes on single links to national road networks. Tolls can be differentiated by time of day, road type and vehicle characteristics, and even set in real time according to current traffic conditions. Conventional toll booths have largely given way to electronic toll collection technologies. The main technology categories are roadside-only systems employing digital photography, tag & beacon systems that use short-range microwave technology, and in-vehicle-only systems based on either satellite or cellular network communications. The best technology choice depends on the application. The rate at which congestion pricing is implemented, and its ultimate scope, will depend on what technology is used and on what other functions and services it can perform. © 2011 Elsevier Ltd.
Masse L.C.,University of British Columbia
Journal of physical activity & health | Year: 2012
Over the years, self-report measures of physical activity (PA) have been employed in applications for which their use was not supported by the validity evidence. To address this concern this paper 1) provided an overview of the sources of validity evidence that can be assessed with self-report measures of PA, 2) discussed the validity evidence needed to support the use of self-report in certain applications, and 3) conducted a case review of the 7-day PA Recall (7-d PAR). This paper discussed 5 sources of validity evidence, those based on: test content; response processes; behavioral stability; relations with other variables; and sensitivity to change. The evidence needed to use self-report measures of PA in epidemiological, surveillance, and intervention studies was presented. These concepts were applied to a case review of the 7-d PAR. The review highlighted the utility of the 7-d PAR to produce valid rankings. Initial support, albeit weaker, for using the 7-d PAR to detect relative change in PA behavior was found. Overall, self-report measures can validly rank PA behavior but they cannot adequately quantify PA. There is a need to improve the accuracy of self-report measures of PA to provide unbiased estimates of PA.
Zaidman-Zait A.,University of British Columbia
Journal of child psychology and psychiatry, and allied disciplines | Year: 2010
The Parenting Stress Index-Short Form (PSI-SF) is one of the most widely used instruments for measuring parenting stress in families of children with autism spectrum disorders (ASD). However, no research to date has examined the psychometric properties of the PSI-SF in a sample of parents of young children with ASD. In this regard, item response theory (IRT) can be used to estimate how much information or discrimination each item of a scale offers across the entire range of the latent variable being measured, by creating individual item information curves or profiles. The purpose of this study was to use IRT to examine the discriminability of PSI-SF items in a sample of parents of young children with ASD who experience varying levels of parental stress. The study involved the parents of 141 children with autism spectrum disorders (91.4% mothers; mean age 36.2 years) who completed the PSI-SF following diagnosis. Item characteristic curves were constructed for each of the PSI-SF items and examined with regard to item functioning. Results indicated that, for the most part, changes in parental distress severity were reflected in changes on item scores. However, several items on the subscales measuring parent-child dysfunctional interactions and child behavior difficulty functioned poorly to discriminate parents across a range of total stress severity. The parent-child dysfunctional interaction and difficult child subscales of the PSI-SF scale should be used with caution with parents of young children with ASD. More research is required to examine PSI-SF content validity, at least among parents of children with ASD and perhaps parents of children with other disabilities as well. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.
Enright A.,University of British Columbia
Canadian Journal of Anesthesia | Year: 2013
Purpose: Improving patient safety during anesthesia and surgery is the focus of much effort worldwide. Major advances have occurred since the 1980s, especially in economically advantaged areas. This paper is a review of some of the challenges that face those who work in resource-poor areas of the world. Principal findings: There is a shortage of trained anesthesia providers, both physician and non-physician, and this is particularly acute outside urban areas. Anesthesia is still sometimes delivered by unqualified people, which results in expected high rates of morbidity and mortality. Residency training programs in low-income countries ought to increase their output as anesthesiologists must be available to supervise non-physician providers. All groups require continuing medical education. In addition, increased efforts are needed to recruit trainees into the specialty of anesthesia and to retain them locally. There is a well-recognized shortage of resources for anesthesia. Consequently, concerted efforts are necessary to ensure reliable supplies of drugs, and attention should be paid to the procurement of anesthesia equipment appropriate for the location. Biomedical support must also be developed. Lifebox is a charitable foundation dedicated to supplying pulse oximeters to low- and middle-income countries. Adoption of the World Health Organization's Surgical Safety Checklist could further reduce morbidity and mortality. Conclusions: Much time, effort, planning, and resources are required to ensure that anesthesia in low-income areas can reach internationally accepted standards. Such investment in anesthesia would result in wider access to surgical and obstetrical care, and the quality and safety of that care would be much improved. © 2012 Canadian Anesthesiologists' Society.
Krishnamurthy V.,University of British Columbia |
Vincent Poor H.,Princeton University
IEEE Signal Processing Magazine | Year: 2013
How do local agents and global decision makers interact in statistical signal processing problems where autonomous decisions need to be made? When individual agents possess limited sensing, computation, and communication capabilities, can a network of agents achieve sophisticated global behavior? Social learning and Bayesian games are natural settings for addressing these questions. This article presents an overview, novel insights, and a discussion of social learning and Bayesian games in adaptive sensing problems when agents communicate over a network. Two highly stylized examples that demonstrate to the reader the ubiquitous nature of the models, algorithms, and analysis in statistical signal processing are discussed in tutorial fashion. © 1991-2012 IEEE.
Stoessl A.J.,University of British Columbia
Neurotherapeutics | Year: 2011
Summary: Parkinson's disease (PD) is a common disorder in which the primary features can be related to dopamine deficiency. Changes on structural imaging are limited, but a wealth of abnormalities can be detected using positron emission tomography, single photon emission computed tomography, or functional magnetic resonance imaging to detect changes in neurochemical pathology or functional connectivity. The changes detected on these studies may reflect the disease process itself and/or compensatory responses to the disease, or they may arise in association with disease- and/or treatment-related complications. This review will focus mainly on neurochemical and metabolic studies and reviews various approaches to the assessment of dopaminergic function as well as the function of other neurotransmitters that may be affected in PD. A number of clinical applications are highlighted, including diagnostic utility, identification of preclinical disease, changes associated with motor and nonmotor complications of PD, and the effects of various therapeutic interventions. © 2011 The American Society for Experimental NeuroTherapeutics, Inc.
Schulte P.M.,University of British Columbia
Journal of Experimental Biology | Year: 2014
Although the term environmental stress is used across multiple fields in biology, the inherent ambiguity associated with its definition has caused confusion when attempting to understand organismal responses to environmental change. Here I provide a brief summary of existing definitions of the term stress, and the related concepts of homeostasis and allostasis, and attempt to unify them to develop a general framework for understanding how organisms respond to environmental stressors. I suggest that viewing stressors as environmental changes that cause reductions in performance or fitness provides the broadest and most useful conception of the phenomenon of stress. I examine this framework in the context of animals that have evolved in highly variable environments, using the Atlantic killifish, Fundulus heteroclitus, as a case study. Consistent with the extreme environmental variation that they experience in their salt marsh habitats, killifish have substantial capacity for both short-term resistance and long-term plasticity in the face of changing temperature, salinity and oxygenation. There is inter-population variation in the sensitivity of killifish to environmental stressors, and in their ability to acclimate, suggesting that local adaptation can shape the stress response even in organisms that are broadly tolerant and highly plastic. Whole-organism differences between populations in stressor sensitivity and phenotypic plasticity are reflected at the biochemical and molecular levels in killifish, emphasizing the integrative nature of the response to environmental stressors. Examination of this empirical example highlights the utility of using an evolutionary perspective on stressors, stress and stress responses. © 2014. Published by The Company of Biologists Ltd.
Kaur A.,University of British Columbia
Clinical Genetics | Year: 2013
Mutations in GNAL cause primary torsion dystonia Fuchs et al. (2013) Nature Genetics 45: 88-92. © 2013 John Wiley & Sons A/S.
Kabir G.,University of British Columbia
International Journal of Fuzzy System Applications | Year: 2012
A systematic approach to the inventory control and classification may have significant influence on company competitiveness. In practice, all inventories cannot be controlled with equal attention. In order control the inventory items and to determine the suitable ordering policies for them, multiple criteria inventory classification is used. A systematic and logical approach is structured for multiple criteria inventory classification under fuzzy environment through integrating Fuzzy Delphi Method (FDM) with Fuzzy Analytic Hierarchy Process (FAHP). Fuzzy Delphi method is used to identify the important criteria and, Fuzzy AHP is used to determine the relative weights of the criteria, and to classify inventories into different categories. To accredit the proposed model, its implemented for the 351 raw materials of switch gear section of Energypac Engineering Limited (EEL), a large power engineering company of Bangladesh. Copyright © 2012, IGI Global.
Drew B.,University of British Columbia
Journal of magnetic resonance imaging : JMRI | Year: 2010
To develop a device for sectioning prostatectomy specimens that would facilitate comparison between histology and in vivo MRI. A multi-bladed cutting device was developed, which consists of an adjustable box capable of accommodating a prostatectomy specimen up to 85 mm in size in the lateral direction, a "plunger" tool to press on the excised gland from the top to prevent it from rolling or sliding during sectioning, and a multi-bladed knife assembly capable of holding up to 21 blades at 4-mm intervals. The device was tested on a formalin fixed piece of meat and subsequently used to section a prostatectomy specimen. Histology sections were compared with T2-weighted MR images acquired in vivo before the prostatectomy procedure. The prostatectomy specimen slices were very uniform in thickness with each face parallel to the other with no visible sawing marks on the sections by the blades after the cut. MRI and histology comparison showed good correspondence between the two images. The developed device allows sectioning of prostatectomy specimens into parallel cuts at a specific orientation and fixed intervals. Such a device is useful in facilitating accurate correlation between histology and MRI data.
Thakor A.S.,Stanford University |
Thakor A.S.,University of British Columbia |
Thakor A.S.,University of Cambridge |
Gambhir S.S.,Stanford University
CA Cancer Journal for Clinicians | Year: 2013
In recent years, there has been an unprecedented expansion in the field of nanomedicine with the development of new nanoparticles for the diagnosis and treatment of cancer. Nanoparticles have unique biological properties given their small size and large surface area-to-volume ratio, which allows them to bind, absorb, and carry compounds such as small molecule drugs, DNA, RNA, proteins, and probes with high efficiency. Their tunable size, shape, and surface characteristics also enable them to have high stability, high carrier capacity, the ability to incorporate both hydrophilic and hydrophobic substances and compatibility with different administration routes, thereby making them highly attractive in many aspects of oncology. This review article will discuss how nanoparticles are able to function as carriers for chemotherapeutic drugs to increase their therapeutic index; how they can function as therapeutic agents in photodynamic, gene, and thermal therapy; and how nanoparticles can be used as molecular imaging agents to detect and monitor cancer progression. CA Cancer J Clin 2013;63:395-418. © 2013 American Cancer Society, Inc.
Lee J.W.,University of British Columbia
Clinical Genetics | Year: 2013
A recurrent PDGFRB mutation causes familial infantile myofibromatosis Cheung et al. (2013) The American Journal of Human Genetics 92: 996-1000. Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis Martignetti et al. (2013) The American Journal of Human Genetics 92: 1001-1007. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Bell K.,University of British Columbia
BioSocieties | Year: 2013
Over the past two decades, molecular technologies have transformed the landscape of cancer diagnosis, treatment and disease surveillance. However, although the effects of these technologies in the areas of primary and secondary cancer prevention have been the focus of growing study, their role in tertiary prevention remains largely unexamined. Treating this topic as a problematic to be conceptually explored rather than empirically demonstrated, this article focuses on the molecularisation of tertiary prevention, especially the growing use of molecular biomarkers to monitor disease recurrence. Taking a semiotic approach, I speculate on the potential meanings of molecular biomarkers for people living with and beyond cancer and suggest the meanings of these technologies may differ in important ways for those on both sides of the risk divide: that is, those 'at risk' for cancer and those living with realised risk. Although molecular biomarkers may intensify a sense of 'measured vulnerability', by indexing cancer's presence they may also prove reassuring. Moreover, as an invisible but ostensibly 'transparent' sign, in some contexts they appear to enable cancer survivors to challenge biomedical decision making. In the light of recent oncological debates about the value of these biomarkers in tertiary prevention, I conclude by suggesting that signs can never be reduced to their 'objective' biomedical denotation in spite of professional attempts to expunge meaning and value from care. © 2013 Macmillan Publishers Ltd.
Chen H.M.,National Taiwan University |
Chen C.K.,National Taiwan University |
Liu R.-S.,National Taiwan University |
Zhang L.,NRC Institute for Fuel Cell Innovation |
And 2 more authors.
Chemical Society Reviews | Year: 2012
This review concerns the efficient conversion of sunlight into chemical fuels through the photoelectrochemical splitting of water, which has the potential to generate sustainable hydrogen fuel. In this review, we discuss various photoelectrode materials and relative design strategies with their associated fabrication for solar water splitting. Factors affecting photoelectrochemical performance of these materials and designs are also described. The most recent progress in the research and development of new materials as well as their corresponding photoelectrodes is also summarized in this review. Finally, the research strategies and future directions for water splitting are discussed with recommendations to facilitate the further exploration of new photoelectrode materials and their associated technologies. © The Royal Society of Chemistry 2012.
Stamp P.C.E.,University of British Columbia
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012
We review the difference between standard environmental decoherence and 'intrinsic decoherence', which is taken to be an ineluctable process of Nature. Environmental decoherence is typically modelled by spin bath or oscillator modes-we review some of the unanswered questions not captured by these models, and also the application of them to experiments. Finally, a sketch is given of a new theoretical approach to intrinsic decoherence, and this scheme is applied to the discussion of gravitational decoherence. © 2012 The Royal Society.
Raussendorf R.,University of British Columbia
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012
In this introductory article on the subject of quantum error correction and faulttolerant quantum computation, we review three important ingredients that enter known constructions for fault-tolerant quantum computation, namely quantum codes, error discretization and transversal quantum gates. Taken together, they provide a ground on which the theory of quantum error correction can be developed and fault-tolerant quantum information protocols can be built. © 2012 The Royal Society.
Redfield R.J.,University of British Columbia
Trends in Genetics | Year: 2015
The personal and societal importance of genetics has increased dramatically since the 1950s, but most introductory courses still focus on teaching students how to think like geneticists, training them in Mendelian and molecular analysis. This article is a personal account of a new course with a different goal, giving students knowledge and skills that they can use in their nonacademic lives. Useful Genetics differs from typical courses in emphasizing personal genomics, natural genetic and phenotypic variation in humans, and the consequences of genetic inheritance for breeding, inbreeding, and ancestry. Although it is a Massive Open Online Course (MOOC), taught to large global populations of learners of all ages and backgrounds, it maintains the academic rigor of a college course. The course materials are freely available for reuse by other instructors, and are being used as the foundation of a face-to-face university credit course. © 2015 Elsevier Ltd.
Lim K.F.,University of British Columbia